The cholinergic system plays an important role in the central nervous system of insects and is closely related to the complex behavior of insects. The immunohistochemical technique was performed to detect the expressi...The cholinergic system plays an important role in the central nervous system of insects and is closely related to the complex behavior of insects. The immunohistochemical technique was performed to detect the expression of like-muscarinic acetylcholine receptor M2 in the brain of three castes of Polyrhachis vicina. A positive expression of like-muscarinic acetylcholine receptor M2 was observed in the mushroom body, central body and antennal lobes of the ant brain; but there is great diversity in their location and intensity among worker, queen and male ants. It is speculated that like-muscafinic acetylcholine receptor M2 plays a critical role in the central nervous system, in terms of projecting visual information and olfactory information into the protocerebrum and integrating many inputs.展开更多
Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physi...Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.展开更多
The antibodies against acetylcholine receptor AchR and levels of SOD and LPO were measured in 11 patients with myasthenia gravis (MG),and the results were compared with normal controls and patients with diseases other...The antibodies against acetylcholine receptor AchR and levels of SOD and LPO were measured in 11 patients with myasthenia gravis (MG),and the results were compared with normal controls and patients with diseases other than MG.The results showed that the antibodies against AchR were higher as compared with other groups before and after operation. The post-operative level of antibodies was obviously lower than the pre-operative value. An slight increase in SOD and significant decrease in mean value of LPO after surgery were noted. The possible mechanism was discussed.展开更多
To find promising new multitargeted AD (Alzheimer's disease) inhibitors, the 3D-QSAR (three-dimensional quantitative structure-activity relationship) model for 32 AD inhibitors was established by using the CoMFA ...To find promising new multitargeted AD (Alzheimer's disease) inhibitors, the 3D-QSAR (three-dimensional quantitative structure-activity relationship) model for 32 AD inhibitors was established by using the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity index analysis) methods. Results showed that the CoMFA and CoMSIA models were constructed successfully with a good cross-validated coefficient (q2) and a non-cross-validated coefficient (R2), and the binding modes obtained by molecular docking were in agreement with the 3D-QSAR results, which suggests that the present 3D-QSAR model has good predictive capability to guide the design and structural modification of novel multitargeted AD inhibitors. Meanwhile, we found that one side of inhibitory molecule should be small group so that it would be conductive to enter the gorge to interact with the catalytic active sites of AChE (acetylcholinesterase), and the other side of inhibitory molecule should be large group so that it would be favorable for interaction with the peripheral anionic site of ACHE. Furthermore, based on the 3D-QSAR model and the binding modes of AChE and [3-secretase (BACE-1), the designed molecules could both act on dual binding sites of AChE (catalytic and peripheral sites) and dual targets (ACHE and BACE-1). We hope that our results could provide hints for the design of new multitargeted AD derivatives with more potency and selective activity.展开更多
Nicotinic acetylcholine receptors (nAChRs) play a significant role in excitatory synaptic transmission in insects and are the target for chloronicotinyl and nereistoxin insecticides.In recent years,Chilo suppressalis,...Nicotinic acetylcholine receptors (nAChRs) play a significant role in excitatory synaptic transmission in insects and are the target for chloronicotinyl and nereistoxin insecticides.In recent years,Chilo suppressalis,an economically important pest of rice,developed high resistance against monosultap,a nereistoxin insecticide acting on nAChR.In order to reveal the hypothesized target insensitive mechanism,studies on the molecular property of nAChR from Chilo suppressalis are required.In this study,the full length cDNA of nAChR α subunit from this pest was cloned by RT-PCR.Sequence analysis shows that it is a novel nAChR α subunit,which was named as Cs α 1(Genbank accession No.AF418987).It contains 1?997?bp nucleotides and involves an open reading frame (ORF) encoding a mature protein of 509 amino acids excluding a signal peptide of 24 amino acids.The deduced amino acid sequence was 52%-94% identical to the reported insect nAChR genes.展开更多
Objective To observe the effect of moxibustion of Baihui(百会GV20) and Shenshu(肾俞 BL 23) on acetylcholine (AOh) content and choline acetyl transferase (CHAT) activity in the brain of aging rats so as to inve...Objective To observe the effect of moxibustion of Baihui(百会GV20) and Shenshu(肾俞 BL 23) on acetylcholine (AOh) content and choline acetyl transferase (CHAT) activity in the brain of aging rats so as to investigate its underlying mechanism in delaying brain aging in the rat. Methods Thirty Wistar rats including 10 young rats (young group) and 20 aged rats that were divided into aging group and moxibustion group evenly, were used in this study. For rats of moxibustion group, moxibustion was applied to Baihui (百会GV20) and Shenshu(肾俞 BL23) for 10 min, once a day, with 5 days being a course of treatment, 8 courses altogether. At the end of the experiments, the rats anesthetized with 6 % chloral hydrate were decapitated for taking brain tissue, then AOh content, CHAT and acetylcholinesterase (ACHE) activity were detected by using high performance liquid chromatography (HPLC). Results Compared with young rat group, AOh contents of basal ganglia, hippocampus and cerebral cortex tissues in aging group and moxibustion group all decreased significantly (P〈 0.05, 0.01 ), while compared with aging group, ACh contents in the 3 cerebral regions in moxibustion group all increased considerably (P〈0.01). In comparison with young group, both CHAT activity and AChE activity of the brain tissue in aging group and moxibustion group lowered significantly ( P 〈 0.05, 0.01 ) ; comparison between aging group and moxibustion group showed that CHAT activity of the later group increased evidently (P〈 0.05) while AChE activity in moxibustion group decreased considerably (P〈0.01), displaying that moxibustion could potentiate CHAT activity and further lower AChE activity of the brain in aged rats. Conclusion Moxibustion of Baihui(百会GV20) and Shenshu(肾俞 BL23) has effects in raising AOh contents and lowering CHAT and AChE activity, which may contribute to its efficacies in repairing the injured central cholinergic nerve system and delaying the aging process in the aged rats.展开更多
Acetylcholine (Ach) is a key component of animal cholinergic system. Recent experiments demonstrated that Ach, choline acetyltransferase, acetylcholinesterase and Ach receptors are present in all parts of plants and...Acetylcholine (Ach) is a key component of animal cholinergic system. Recent experiments demonstrated that Ach, choline acetyltransferase, acetylcholinesterase and Ach receptors are present in all parts of plants and have many functions, including inducing stomatal movement. The authors' previous work has evidenced that microtubules and microfilaments are involved in regulating both stomatal closing and opening. The present investigation is to determine whether stomatal opening induced by Ach is associated with microtubules and microfilaments. The results showed that Ach could induce stomatal opening of Vicia faba L. with or without addition of KCl in the dark. Ach also stimulated protoplast swelling in a K +_free solution in the dark. However, the induction was partially suppressed when the strips and protoplasts were pretreated with either cytochalasin B, an inhibitor of F_actin polymerization, or oryzalin, an inhibitor of plant microtubule polymerization. Thus, our data suggest for the first time that stomatal opening induced by Ach is associated with the dynamics of microtubules and microfilaments.展开更多
Objective To examine the effect of acetylcholine(ACh)on the electric activities of pain-excitation neurons (PEN)and pain-inhibitation neurons(PIN)in the hippocampal CA1 area of normal rats or morphinistic rats,a...Objective To examine the effect of acetylcholine(ACh)on the electric activities of pain-excitation neurons (PEN)and pain-inhibitation neurons(PIN)in the hippocampal CA1 area of normal rats or morphinistic rats,and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.Methods The trains of electric impulses applied to sciatic nerve were set as noxious stimulation.The discharges of PEN and PIN in the CA l area were recorded extracellularly by glass microelectrode.We observed the influence of intracerebroventricular (i.c.v.)injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.Results Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats.In normal rats,ACh decrease the pain-evoked discharge frequency of PEN,while increased the frequency of PIN.These effects reached the peak value at 4 min after injection of ACh.In morphinistic rats,ACh also inhibited the PEN electric activity and potentialized the PIN electric activity,but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.Conclusion Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation.Morphine addiction attenuated the sensitivity of painrelated neurons to the noxious information.展开更多
Sepsis-associated encephalopathy(SAE) is a brain dysfunction that occurs secondary to infection in the bo characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological sign...Sepsis-associated encephalopathy(SAE) is a brain dysfunction that occurs secondary to infection in the bo characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. S involves a number of mechanisms, including neuroinflammation, in which the interaction between cytokines a acetylcholine results in neuronal loss and alterations in cholinergic signaling. Moreover, the interaction also occurs the periphery, accelerating a type of immunosuppressive state. Although its diagnosis is not specific in biochemis and imaging tests, it could potentiate severe outcomes, including increased mortality, cognitive decline, progress immunosuppression, cholinergic anti-inflammatory deficiency, and even metabolic and hydroelectrolyte imbalan Therefore, the bilateral communication between SAE and the multiple peripheral organs and especially the immu system should be emphasized in sepsis management.展开更多
The combinative rate measurement of (3-[I125] iodotyrosyl) α-bungarotoxin was applied in the analysis of the relation between nerve acetylcholine receptor and three types of insecticide resistance in diamondback mo...The combinative rate measurement of (3-[I125] iodotyrosyl) α-bungarotoxin was applied in the analysis of the relation between nerve acetylcholine receptor and three types of insecticide resistance in diamondback moth, Plutella xylostella (L.). In the dimehypo-resistant strain and in the cartap-resistant strain, the nerve acetylcholine receptor showed the remarkable insensitivity to dimehypo and cartap, of which the binding rate to ligand was approximately 66 and 60%, respectively, of the susceptible strain. The sensitivity to deltamethrin in the deltamethrin-resistant strain did not show visible change. These results indicated that the decline in the sensitivity of nerve acetylcholine receptor to insecticide might be a potential mechanism to nereistoxin insecticides resistance in the diamondback moth.展开更多
Traumatic brain injury (TBI) poses a significant socioeconomic burden in the world. The long lasting consequences in cognitive impairments are often underreported and its mechanisms are unclear. In this perspective,...Traumatic brain injury (TBI) poses a significant socioeconomic burden in the world. The long lasting consequences in cognitive impairments are often underreported and its mechanisms are unclear. In this perspective, cholinergic dysfunction and thera-peutic strategy targeting this will be reviewed. Novel agents that can target specific subtype of acetylcholine receptors have been developed over the recent years and are at various stages of development, which include AR-R 17779, GTS-21, SSR- 180711A, AR-R17779, and PNU-282987. A detailed review on this topic has been previously published (Shin and Dixon, 2015).展开更多
AIM: To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor(mAChR) M1 in the eyes of guinea pigs.METHODS: Thirty guinea pigs(15-20 days ...AIM: To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor(mAChR) M1 in the eyes of guinea pigs.METHODS: Thirty guinea pigs(15-20 days old) were randomly divided into three groups(n=10/group). Animals in group I were raised in a completely closed carton with green flickering light illumination. Those in group II were kept in the open top closed carton under normal natural light. Guinea pigs were raised in a sight-widen cage under normal natural light in group III. The refractive status and axial length were measured before and after 8 weeks' illumination. Moreover, total RNA extracted from retinal, choroidal, and scleral tissues were determined by real-time reverse transcription polymerase chain reaction(RT-PCR). The expressions of the receptor M1 were also explored in the retina, choroid, and sclera using immunohistochemistry.RESULTS: There was a remarkable reduction in refractive error and increase in axial length after 8-weeks' green flickering light stimulation(P〈0.001). The expression of M1 receptor mRNA in sclera and retina in myopia group were remarkably lower than that in group II and III(P〈0.01). Significant reduced expression of M1 receptor stimulated by green flickering light in retina and sclera tissues were also observed(P〈0.05). However, there was no M1 receptor expression in choroid in 3 groups.CONCLUSION: Myopia can be induced by 8 weeks' green flickering light exposure in the animal model. M1 receptor may be involved causally or protectively in myopia development.展开更多
The present study found expressions of a7 nicotinic acetylcholine receptor on hippocampal slices and hippocampal astrocytes using double immunofluorescence stainings. Expression of glial fibdllary acidic protein in th...The present study found expressions of a7 nicotinic acetylcholine receptor on hippocampal slices and hippocampal astrocytes using double immunofluorescence stainings. Expression of glial fibdllary acidic protein in the cultured hippocampal slices and hippocampal astrocytes significantly increased, and levels of macrophage inflammatory protein la, RANTES, interleukin-1β, intedeukin-6, and tumor necrosis factor-α increased in the supernatant of cultured astrocytes following exposure to 200 nM amyloid 13 protein 1-42. Preconditioning of 10 μM nicotine, a nicotinic acetylcholine receptor agonist, could attenuate the influence of amyloid β protein 1-42 in inflammatory mediator secretion of cultured astrocytes. Experimental findings indicated that α7 nicotinic acetylcholine receptor was expressed on the surface of hippocampal astrocytes, and activated a7 nicotinic acetylcholine receptor was shown to inhibit inflammation induced by amyloid β protein 1-42.展开更多
BACKGROUND: The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase (ACHE) and monoa...BACKGROUND: The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase (ACHE) and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis polysaccharide has an anti-aging effect. OBJECTIVE: To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING: Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003. MATERIALS: Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical (batch No. 20030804; state drug permit No. H21023095). A total of 50 six-week-old Kunming mice were randomly divided into five groups: blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS: Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution (0.5 mL/20 g) in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution (0.2 mL/10 g), respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension (0.2 mL/10 g), and the mice in the model group were intragastrically infused with the same volume of normal saline (0.2 mL/10 g) once per day for 30 consecutive days. MAIN OUTCOME MEASURES: Two hours after the final administration, pathohistological changes in the cerebral cortex and hippocampus were observed using hematoxylin & eosin staining. AChE activity was detected using chromatometry. Monoamine neurotransmitter content was measured using fluorimetry. Learning and memory was measured using the step down test and darkness avoidance test. RESULTS: Both Schisandra chinensis polysaccharide and Kangnaoling improved pathological injury to the cerebral cortex and hippocampus in a mouse model of brain aging. Compared with the blank control group, AChE activity and content of norepinephrine (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were significantly decreased in the model group (P 〈 0.01 ). In contrast, AChE activity and NA, DA, and 5-HT levels significantly increased in the Kangnaoling and high dosage Schisandra chinensis polysaccharide groups (P 〈 0.01), while NA levels significantly increased in the low dosage Schisandra chinensis polysaccharide group (P 〈 0.01). Drug treatment improved learning and memory abilities (P 〈 0.01 or P 〈 0.05). CONCLUSION: Schisandra chinensis polysaccharide significantly increased levels of central neurotransmitters and improved learning and memory in a mouse model of brain aging. The effects of Schisandra chinensis polysaccharide were equal to that of Kangnaoling pellets.展开更多
Background Smoking and other risk factors have been well known as important factors of variant angina or coronary artery spasm (CAS). However, clinical features related to age on coronary artery spasm have been rare...Background Smoking and other risk factors have been well known as important factors of variant angina or coronary artery spasm (CAS). However, clinical features related to age on coronary artery spasm have been rarely evaluated. Methods We evaluated 3155 consecutive patients with insignificant coronary artery lesion. Patients underwent Acetylcholine (Ach) provocation test for induction of CAS. CAS was defined as 〉 70% luminal narrowing of coronary arteries during Ach provocation test. The results of Ach provocation test were compared among age groups; 〈 45 years (Group 1), 45-54 years (Group 2), 55-64 years (Group 3), and 〉_ 65 years (Group 4). Results Older patients had higher incidence of hypertension, diabetes, but lower incidence rate of current smoking, male sex compared with younger patients. Positive Ach provocation test finding was frequently showed with aging (47.36% vs. 58.3% vs. 62.6% vs. 61.5%; P 〈 0.001). Multivariate logistic analysis showed that age, male, and myocardial bridge were independent predictors of CAS induced by Ach provocation test. Conclusion Our present study showed that old age was independent predictor for Ach-induced significant coronary artery spasm.展开更多
Umbilical cord mesenchymal stem cells were isolated by a double enzyme digestion method. The third passage of umbilical cord mesenchymal stem cells was induced with heparin and/or basic fi- broblast growth factor. Res...Umbilical cord mesenchymal stem cells were isolated by a double enzyme digestion method. The third passage of umbilical cord mesenchymal stem cells was induced with heparin and/or basic fi- broblast growth factor. Results confirmed that cell morphology did not change after induction with basic fibroblast growth factor alone. However, neuronal morphology was visible, and micro- tubule-associated protein-2 expression and acetylcholine levels increased following induction with heparin alone or heparin combined with basic fibroblast growth factor. Hb9 and choline acetyl- transferase expression was high following inductive with heparin combined with basic fibroblast growth factor. Results indicate that the inductive effect of basic fibroblast growth factor alone was not obvious. Heparin combined with basic fibroblast growth factor noticeably promoted the differen- tiation of umbilical cord mesenchymal stem cells into motor neuron-like cells. Simultaneously, um- bilical cord mesenchymal stem cells could secrete acetylcholine.展开更多
BACKGROUND: Peripheral nerve ischemia has been shown to result in ischemic fiber degenera-tion and axoplasmic transport disturbance. However, the effect on acetylcholinesterase (AChE) ex- pression in relevant cells...BACKGROUND: Peripheral nerve ischemia has been shown to result in ischemic fiber degenera-tion and axoplasmic transport disturbance. However, the effect on acetylcholinesterase (AChE) ex- pression in relevant cells following sciatic nerve ischemia remains unclear. OBJECTIVE: To observe AChE concentration changes following peripheral nerve ischemia. DESIGN, TIME AND SETTING: The present comparative observation, neuroanatomical experiment was performed at the Central Laboratory Animal of Chengde Medical College between 2006 and 2007. MATERIALS: A total of 20 healthy, adult, Wistar rats were randomized into two groups (n = 10): 8-day ischemia and 14-day ischemia. METHODS: Ischemia injury was induced in the unilateral sciatic nerve (experimental side) through ligation of the common iliac artery. The contralateral side received no intervention, and served as the control side. Rats in the 8-day ischemia and 14-day ischemia groups were allowed to survive for 8 and 14 days, respectively. MAIN OUTCOME MEASURES: The L5 lumbar spinal cord and the L5 dorsal root ganglion were removed from both sides and sectioned utilizing a Leica vibrating slicer. AChE cellular expression was detected using Karnovsky-Root, and the number of AChE-positive cells and average gray value were analyzed using a MiVnt image analysis system. RESULTS: In the 8-day ischemia group, AChE-positive cell numbers were significantly less in the dorsal root ganglion and spinal cord anterior horn of the experimental side, but the average gray value was significantly greater, compared with the control side (P 〈 0.05). These changes were more significant in the 14-day ischemia group than in the 8-day ischemia group (P 〈 0.01). CONCLUSION: Peripheral nerve ischemia leads to decreased AChE expression in the associated cells in a time-dependent manner.展开更多
Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through ...Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.展开更多
BACKGROUND: A large number of investigations have shown that acetylcholine (ACh) and the nucleus locus coeruleus (LC) play an important role in the modulation of pain in rats; however, there is no concrete eviden...BACKGROUND: A large number of investigations have shown that acetylcholine (ACh) and the nucleus locus coeruleus (LC) play an important role in the modulation of pain in rats; however, there is no concrete evidence addressing the relationship between ACh injection into the LC and the electrical activities of pain-related neurons in the LC of healthy rats. OBJECTIVE: To study changes in the discharge of pain-related neurons in the LC following injection of ACh, or its M receptor antagonist, atropine, and to investigate the role of ACh and the LC in the pain signaling pathway. DESIGN, TIME AND SETTING: A randomized, controlled, neuroelectrophysiological animal experiment was performed from November 2007 to December 2008, in the Physiological Laboratory of Harbin Medical University, China. MATERIALS: Acetylcholine chloride was obtained from Shanghai San'aisi Reagent Co., Ltd., China atropine was purchased from Tianjin Jinyao Amino Acid Co., Ltd., China. METHODS: This study was divided into two sections as follows: (1) 46 adult Wistar rats were randomly assigned into an ACh group and a control group, with 23 rats in each. (2) 34 adult Wistar rats were randomly assigned to an atropine group and a control group, with 17 rats in each. The sciatic nerve was stimulated by a series of electrical impulses, serving as peripheral noxious stimuli. Electrical changes in pain-related neurons in the LC were measured by glass microelectrodes. The LC of rats in the ACh and atropine groups were injected with 2 μg/μL ACh or 0.5 μg/μL atropine, respectively, in 1 μL volume. Rats in the control groups received injection of 1 pL physiological saline within 4 minutes. MAIN OUTCOME MEASURES: To measure the net increase in the discharge value, latency and complete inhibitory duration of pain-related neurons before and after administration of ACh or atropine. RESULTS: The injection of ACh into the LC increased the pain-evoked discharge frequency and shortened the latency of the pain-excitation neurons. It decreased the pain-evoked discharged frequency and prolonged the inhibitory duration of pain-inhibition neurons. Injection of atropine into LC blocked the effects of ACh. CONCLUSION: ACh strengthened the response of pain-related neurons in LC of rats to noxious stimulation, exhibiting the effects of facilitated pain. This indicates that ACh and LC play an important role in the modulation of algesia.展开更多
Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membra...Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine(ACh) or other biologic compounds including nicotine. n ACh Rs have been found on lung cancer cells, underscoring the idea that the non-neuronal n ACh R pathway has important implications for lung cancer. Several studies focusing on the treatment with n ACh R antagonists with improved selectivity might trigger novel strategies for the intervention and prevention of lung cancer. Here we review the genetic risk factors for lung cancer in the n ACh R gene cluster, the roles of nicotine receptors, and the molecular mechanisms of acetylcholine receptor pathways to lead to more opportunities for intervention and prevention of lung cancer.展开更多
基金the Natural Science Foundation of Shaanxi, China (2005 Cl 25)
文摘The cholinergic system plays an important role in the central nervous system of insects and is closely related to the complex behavior of insects. The immunohistochemical technique was performed to detect the expression of like-muscarinic acetylcholine receptor M2 in the brain of three castes of Polyrhachis vicina. A positive expression of like-muscarinic acetylcholine receptor M2 was observed in the mushroom body, central body and antennal lobes of the ant brain; but there is great diversity in their location and intensity among worker, queen and male ants. It is speculated that like-muscafinic acetylcholine receptor M2 plays a critical role in the central nervous system, in terms of projecting visual information and olfactory information into the protocerebrum and integrating many inputs.
基金National Natural Science Foundation of China(32202800)Natural Science Foundation of Heilongjiang Province(LH2022C104)+1 种基金Heilongjiang Province Education Department Fundamental Scientifc Research Funds(145109516)Qiqihar University Graduate Innovative Research Project(YJSCX2022016).
文摘Background: No other effects of atropine other than as an antagonist of muscarinic acetylcholine receptor (mAChR) have been found. Methods: In this study, human kidneyepithelial cells were treated with different physiological regulators. Results: Subsequently, it was found that atropine could significantly induce autophagy as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm ofhost cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and increased p62/SQSTM1 indicatedincomplete autophagy. In addition, atropine induced autophagosome levels in a dose-dependent manner within a certain concentration range in human kidney epithelial cells. In atropine-treated mouse skeletal muscle cells containing nicotinic acetylcholinereceptors and rat cardiac muscle cells containing mAchR, atropine induced autophagy in mouse skeletal muscle cells but not in rat cardiac muscle cells. Furthermore, atropine did not induce autophagy in tissue cells containing mAchR in vivo but did in tissue cells not containing mAchR. Conclusion: This study expands the application and understanding of atropine’s action mechanism in the field of medicine.
文摘The antibodies against acetylcholine receptor AchR and levels of SOD and LPO were measured in 11 patients with myasthenia gravis (MG),and the results were compared with normal controls and patients with diseases other than MG.The results showed that the antibodies against AchR were higher as compared with other groups before and after operation. The post-operative level of antibodies was obviously lower than the pre-operative value. An slight increase in SOD and significant decrease in mean value of LPO after surgery were noted. The possible mechanism was discussed.
基金Acknowledgments The authors acknowledge the financial support of the Natural Science Foundation of Guangxi Province (No. 2013GXNSFAA019019) and the Natural Science Foundation of Guangxi Province (No. 2013GXNSFAA019041).
文摘To find promising new multitargeted AD (Alzheimer's disease) inhibitors, the 3D-QSAR (three-dimensional quantitative structure-activity relationship) model for 32 AD inhibitors was established by using the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity index analysis) methods. Results showed that the CoMFA and CoMSIA models were constructed successfully with a good cross-validated coefficient (q2) and a non-cross-validated coefficient (R2), and the binding modes obtained by molecular docking were in agreement with the 3D-QSAR results, which suggests that the present 3D-QSAR model has good predictive capability to guide the design and structural modification of novel multitargeted AD inhibitors. Meanwhile, we found that one side of inhibitory molecule should be small group so that it would be conductive to enter the gorge to interact with the catalytic active sites of AChE (acetylcholinesterase), and the other side of inhibitory molecule should be large group so that it would be favorable for interaction with the peripheral anionic site of ACHE. Furthermore, based on the 3D-QSAR model and the binding modes of AChE and [3-secretase (BACE-1), the designed molecules could both act on dual binding sites of AChE (catalytic and peripheral sites) and dual targets (ACHE and BACE-1). We hope that our results could provide hints for the design of new multitargeted AD derivatives with more potency and selective activity.
文摘Nicotinic acetylcholine receptors (nAChRs) play a significant role in excitatory synaptic transmission in insects and are the target for chloronicotinyl and nereistoxin insecticides.In recent years,Chilo suppressalis,an economically important pest of rice,developed high resistance against monosultap,a nereistoxin insecticide acting on nAChR.In order to reveal the hypothesized target insensitive mechanism,studies on the molecular property of nAChR from Chilo suppressalis are required.In this study,the full length cDNA of nAChR α subunit from this pest was cloned by RT-PCR.Sequence analysis shows that it is a novel nAChR α subunit,which was named as Cs α 1(Genbank accession No.AF418987).It contains 1?997?bp nucleotides and involves an open reading frame (ORF) encoding a mature protein of 509 amino acids excluding a signal peptide of 24 amino acids.The deduced amino acid sequence was 52%-94% identical to the reported insect nAChR genes.
文摘Objective To observe the effect of moxibustion of Baihui(百会GV20) and Shenshu(肾俞 BL 23) on acetylcholine (AOh) content and choline acetyl transferase (CHAT) activity in the brain of aging rats so as to investigate its underlying mechanism in delaying brain aging in the rat. Methods Thirty Wistar rats including 10 young rats (young group) and 20 aged rats that were divided into aging group and moxibustion group evenly, were used in this study. For rats of moxibustion group, moxibustion was applied to Baihui (百会GV20) and Shenshu(肾俞 BL23) for 10 min, once a day, with 5 days being a course of treatment, 8 courses altogether. At the end of the experiments, the rats anesthetized with 6 % chloral hydrate were decapitated for taking brain tissue, then AOh content, CHAT and acetylcholinesterase (ACHE) activity were detected by using high performance liquid chromatography (HPLC). Results Compared with young rat group, AOh contents of basal ganglia, hippocampus and cerebral cortex tissues in aging group and moxibustion group all decreased significantly (P〈 0.05, 0.01 ), while compared with aging group, ACh contents in the 3 cerebral regions in moxibustion group all increased considerably (P〈0.01). In comparison with young group, both CHAT activity and AChE activity of the brain tissue in aging group and moxibustion group lowered significantly ( P 〈 0.05, 0.01 ) ; comparison between aging group and moxibustion group showed that CHAT activity of the later group increased evidently (P〈 0.05) while AChE activity in moxibustion group decreased considerably (P〈0.01), displaying that moxibustion could potentiate CHAT activity and further lower AChE activity of the brain in aged rats. Conclusion Moxibustion of Baihui(百会GV20) and Shenshu(肾俞 BL23) has effects in raising AOh contents and lowering CHAT and AChE activity, which may contribute to its efficacies in repairing the injured central cholinergic nerve system and delaying the aging process in the aged rats.
文摘Acetylcholine (Ach) is a key component of animal cholinergic system. Recent experiments demonstrated that Ach, choline acetyltransferase, acetylcholinesterase and Ach receptors are present in all parts of plants and have many functions, including inducing stomatal movement. The authors' previous work has evidenced that microtubules and microfilaments are involved in regulating both stomatal closing and opening. The present investigation is to determine whether stomatal opening induced by Ach is associated with microtubules and microfilaments. The results showed that Ach could induce stomatal opening of Vicia faba L. with or without addition of KCl in the dark. Ach also stimulated protoplast swelling in a K +_free solution in the dark. However, the induction was partially suppressed when the strips and protoplasts were pretreated with either cytochalasin B, an inhibitor of F_actin polymerization, or oryzalin, an inhibitor of plant microtubule polymerization. Thus, our data suggest for the first time that stomatal opening induced by Ach is associated with the dynamics of microtubules and microfilaments.
基金the National Natural Science Foundation of China(No.30240058).
文摘Objective To examine the effect of acetylcholine(ACh)on the electric activities of pain-excitation neurons (PEN)and pain-inhibitation neurons(PIN)in the hippocampal CA1 area of normal rats or morphinistic rats,and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.Methods The trains of electric impulses applied to sciatic nerve were set as noxious stimulation.The discharges of PEN and PIN in the CA l area were recorded extracellularly by glass microelectrode.We observed the influence of intracerebroventricular (i.c.v.)injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.Results Noxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats.In normal rats,ACh decrease the pain-evoked discharge frequency of PEN,while increased the frequency of PIN.These effects reached the peak value at 4 min after injection of ACh.In morphinistic rats,ACh also inhibited the PEN electric activity and potentialized the PIN electric activity,but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.Conclusion Cholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation.Morphine addiction attenuated the sensitivity of painrelated neurons to the noxious information.
基金supported by National Natural Science Foundation of China (81272089, 81130035, 81372054, and 81121004)the National Basic Research Program of China (2012CB518102)the "Twelve-Five Plan" for Military Scientific Foundation (BWS12J050)
文摘Sepsis-associated encephalopathy(SAE) is a brain dysfunction that occurs secondary to infection in the bo characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. S involves a number of mechanisms, including neuroinflammation, in which the interaction between cytokines a acetylcholine results in neuronal loss and alterations in cholinergic signaling. Moreover, the interaction also occurs the periphery, accelerating a type of immunosuppressive state. Although its diagnosis is not specific in biochemis and imaging tests, it could potentiate severe outcomes, including increased mortality, cognitive decline, progress immunosuppression, cholinergic anti-inflammatory deficiency, and even metabolic and hydroelectrolyte imbalan Therefore, the bilateral communication between SAE and the multiple peripheral organs and especially the immu system should be emphasized in sepsis management.
基金the National Natural Science Foundation of China (30160050).
文摘The combinative rate measurement of (3-[I125] iodotyrosyl) α-bungarotoxin was applied in the analysis of the relation between nerve acetylcholine receptor and three types of insecticide resistance in diamondback moth, Plutella xylostella (L.). In the dimehypo-resistant strain and in the cartap-resistant strain, the nerve acetylcholine receptor showed the remarkable insensitivity to dimehypo and cartap, of which the binding rate to ligand was approximately 66 and 60%, respectively, of the susceptible strain. The sensitivity to deltamethrin in the deltamethrin-resistant strain did not show visible change. These results indicated that the decline in the sensitivity of nerve acetylcholine receptor to insecticide might be a potential mechanism to nereistoxin insecticides resistance in the diamondback moth.
文摘Traumatic brain injury (TBI) poses a significant socioeconomic burden in the world. The long lasting consequences in cognitive impairments are often underreported and its mechanisms are unclear. In this perspective, cholinergic dysfunction and thera-peutic strategy targeting this will be reviewed. Novel agents that can target specific subtype of acetylcholine receptors have been developed over the recent years and are at various stages of development, which include AR-R 17779, GTS-21, SSR- 180711A, AR-R17779, and PNU-282987. A detailed review on this topic has been previously published (Shin and Dixon, 2015).
基金Supported by Qilu Hospital of Shandong University (No.201805049)
文摘AIM: To investigate the effects of green flickering light on refractive development and expression of muscarinic acetylcholine receptor(mAChR) M1 in the eyes of guinea pigs.METHODS: Thirty guinea pigs(15-20 days old) were randomly divided into three groups(n=10/group). Animals in group I were raised in a completely closed carton with green flickering light illumination. Those in group II were kept in the open top closed carton under normal natural light. Guinea pigs were raised in a sight-widen cage under normal natural light in group III. The refractive status and axial length were measured before and after 8 weeks' illumination. Moreover, total RNA extracted from retinal, choroidal, and scleral tissues were determined by real-time reverse transcription polymerase chain reaction(RT-PCR). The expressions of the receptor M1 were also explored in the retina, choroid, and sclera using immunohistochemistry.RESULTS: There was a remarkable reduction in refractive error and increase in axial length after 8-weeks' green flickering light stimulation(P〈0.001). The expression of M1 receptor mRNA in sclera and retina in myopia group were remarkably lower than that in group II and III(P〈0.01). Significant reduced expression of M1 receptor stimulated by green flickering light in retina and sclera tissues were also observed(P〈0.05). However, there was no M1 receptor expression in choroid in 3 groups.CONCLUSION: Myopia can be induced by 8 weeks' green flickering light exposure in the animal model. M1 receptor may be involved causally or protectively in myopia development.
基金supported by the National Natural Science Foundation of China,No.30471928 and No.30973162the Natural Science Foundation of Guangdong Province,No.07005203
文摘The present study found expressions of a7 nicotinic acetylcholine receptor on hippocampal slices and hippocampal astrocytes using double immunofluorescence stainings. Expression of glial fibdllary acidic protein in the cultured hippocampal slices and hippocampal astrocytes significantly increased, and levels of macrophage inflammatory protein la, RANTES, interleukin-1β, intedeukin-6, and tumor necrosis factor-α increased in the supernatant of cultured astrocytes following exposure to 200 nM amyloid 13 protein 1-42. Preconditioning of 10 μM nicotine, a nicotinic acetylcholine receptor agonist, could attenuate the influence of amyloid β protein 1-42 in inflammatory mediator secretion of cultured astrocytes. Experimental findings indicated that α7 nicotinic acetylcholine receptor was expressed on the surface of hippocampal astrocytes, and activated a7 nicotinic acetylcholine receptor was shown to inhibit inflammation induced by amyloid β protein 1-42.
基金Support Program for New Century Excellent Talents in the National Ministry of Education,No. NCET-04-0657Henan Project for cultivation of Innovation Talents in Colleges and Universities No.2004-23
文摘BACKGROUND: The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase (ACHE) and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis polysaccharide has an anti-aging effect. OBJECTIVE: To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING: Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003. MATERIALS: Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical (batch No. 20030804; state drug permit No. H21023095). A total of 50 six-week-old Kunming mice were randomly divided into five groups: blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS: Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution (0.5 mL/20 g) in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution (0.2 mL/10 g), respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension (0.2 mL/10 g), and the mice in the model group were intragastrically infused with the same volume of normal saline (0.2 mL/10 g) once per day for 30 consecutive days. MAIN OUTCOME MEASURES: Two hours after the final administration, pathohistological changes in the cerebral cortex and hippocampus were observed using hematoxylin & eosin staining. AChE activity was detected using chromatometry. Monoamine neurotransmitter content was measured using fluorimetry. Learning and memory was measured using the step down test and darkness avoidance test. RESULTS: Both Schisandra chinensis polysaccharide and Kangnaoling improved pathological injury to the cerebral cortex and hippocampus in a mouse model of brain aging. Compared with the blank control group, AChE activity and content of norepinephrine (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were significantly decreased in the model group (P 〈 0.01 ). In contrast, AChE activity and NA, DA, and 5-HT levels significantly increased in the Kangnaoling and high dosage Schisandra chinensis polysaccharide groups (P 〈 0.01), while NA levels significantly increased in the low dosage Schisandra chinensis polysaccharide group (P 〈 0.01). Drug treatment improved learning and memory abilities (P 〈 0.01 or P 〈 0.05). CONCLUSION: Schisandra chinensis polysaccharide significantly increased levels of central neurotransmitters and improved learning and memory in a mouse model of brain aging. The effects of Schisandra chinensis polysaccharide were equal to that of Kangnaoling pellets.
文摘Background Smoking and other risk factors have been well known as important factors of variant angina or coronary artery spasm (CAS). However, clinical features related to age on coronary artery spasm have been rarely evaluated. Methods We evaluated 3155 consecutive patients with insignificant coronary artery lesion. Patients underwent Acetylcholine (Ach) provocation test for induction of CAS. CAS was defined as 〉 70% luminal narrowing of coronary arteries during Ach provocation test. The results of Ach provocation test were compared among age groups; 〈 45 years (Group 1), 45-54 years (Group 2), 55-64 years (Group 3), and 〉_ 65 years (Group 4). Results Older patients had higher incidence of hypertension, diabetes, but lower incidence rate of current smoking, male sex compared with younger patients. Positive Ach provocation test finding was frequently showed with aging (47.36% vs. 58.3% vs. 62.6% vs. 61.5%; P 〈 0.001). Multivariate logistic analysis showed that age, male, and myocardial bridge were independent predictors of CAS induced by Ach provocation test. Conclusion Our present study showed that old age was independent predictor for Ach-induced significant coronary artery spasm.
文摘Umbilical cord mesenchymal stem cells were isolated by a double enzyme digestion method. The third passage of umbilical cord mesenchymal stem cells was induced with heparin and/or basic fi- broblast growth factor. Results confirmed that cell morphology did not change after induction with basic fibroblast growth factor alone. However, neuronal morphology was visible, and micro- tubule-associated protein-2 expression and acetylcholine levels increased following induction with heparin alone or heparin combined with basic fibroblast growth factor. Hb9 and choline acetyl- transferase expression was high following inductive with heparin combined with basic fibroblast growth factor. Results indicate that the inductive effect of basic fibroblast growth factor alone was not obvious. Heparin combined with basic fibroblast growth factor noticeably promoted the differen- tiation of umbilical cord mesenchymal stem cells into motor neuron-like cells. Simultaneously, um- bilical cord mesenchymal stem cells could secrete acetylcholine.
文摘BACKGROUND: Peripheral nerve ischemia has been shown to result in ischemic fiber degenera-tion and axoplasmic transport disturbance. However, the effect on acetylcholinesterase (AChE) ex- pression in relevant cells following sciatic nerve ischemia remains unclear. OBJECTIVE: To observe AChE concentration changes following peripheral nerve ischemia. DESIGN, TIME AND SETTING: The present comparative observation, neuroanatomical experiment was performed at the Central Laboratory Animal of Chengde Medical College between 2006 and 2007. MATERIALS: A total of 20 healthy, adult, Wistar rats were randomized into two groups (n = 10): 8-day ischemia and 14-day ischemia. METHODS: Ischemia injury was induced in the unilateral sciatic nerve (experimental side) through ligation of the common iliac artery. The contralateral side received no intervention, and served as the control side. Rats in the 8-day ischemia and 14-day ischemia groups were allowed to survive for 8 and 14 days, respectively. MAIN OUTCOME MEASURES: The L5 lumbar spinal cord and the L5 dorsal root ganglion were removed from both sides and sectioned utilizing a Leica vibrating slicer. AChE cellular expression was detected using Karnovsky-Root, and the number of AChE-positive cells and average gray value were analyzed using a MiVnt image analysis system. RESULTS: In the 8-day ischemia group, AChE-positive cell numbers were significantly less in the dorsal root ganglion and spinal cord anterior horn of the experimental side, but the average gray value was significantly greater, compared with the control side (P 〈 0.05). These changes were more significant in the 14-day ischemia group than in the 8-day ischemia group (P 〈 0.01). CONCLUSION: Peripheral nerve ischemia leads to decreased AChE expression in the associated cells in a time-dependent manner.
文摘Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.
基金the National Natural Science Foundation of China,No.30240058
文摘BACKGROUND: A large number of investigations have shown that acetylcholine (ACh) and the nucleus locus coeruleus (LC) play an important role in the modulation of pain in rats; however, there is no concrete evidence addressing the relationship between ACh injection into the LC and the electrical activities of pain-related neurons in the LC of healthy rats. OBJECTIVE: To study changes in the discharge of pain-related neurons in the LC following injection of ACh, or its M receptor antagonist, atropine, and to investigate the role of ACh and the LC in the pain signaling pathway. DESIGN, TIME AND SETTING: A randomized, controlled, neuroelectrophysiological animal experiment was performed from November 2007 to December 2008, in the Physiological Laboratory of Harbin Medical University, China. MATERIALS: Acetylcholine chloride was obtained from Shanghai San'aisi Reagent Co., Ltd., China atropine was purchased from Tianjin Jinyao Amino Acid Co., Ltd., China. METHODS: This study was divided into two sections as follows: (1) 46 adult Wistar rats were randomly assigned into an ACh group and a control group, with 23 rats in each. (2) 34 adult Wistar rats were randomly assigned to an atropine group and a control group, with 17 rats in each. The sciatic nerve was stimulated by a series of electrical impulses, serving as peripheral noxious stimuli. Electrical changes in pain-related neurons in the LC were measured by glass microelectrodes. The LC of rats in the ACh and atropine groups were injected with 2 μg/μL ACh or 0.5 μg/μL atropine, respectively, in 1 μL volume. Rats in the control groups received injection of 1 pL physiological saline within 4 minutes. MAIN OUTCOME MEASURES: To measure the net increase in the discharge value, latency and complete inhibitory duration of pain-related neurons before and after administration of ACh or atropine. RESULTS: The injection of ACh into the LC increased the pain-evoked discharge frequency and shortened the latency of the pain-excitation neurons. It decreased the pain-evoked discharged frequency and prolonged the inhibitory duration of pain-inhibition neurons. Injection of atropine into LC blocked the effects of ACh. CONCLUSION: ACh strengthened the response of pain-related neurons in LC of rats to noxious stimulation, exhibiting the effects of facilitated pain. This indicates that ACh and LC play an important role in the modulation of algesia.
基金Supported by Youth Foundation of Shanghai Municipal Public Health Bureau,No.20124Y114Shanghai Chest Hospital"1050 Talents Project",ChinaProject of Shanghai Chest Hospital,No.YZ13-16
文摘Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine(ACh) or other biologic compounds including nicotine. n ACh Rs have been found on lung cancer cells, underscoring the idea that the non-neuronal n ACh R pathway has important implications for lung cancer. Several studies focusing on the treatment with n ACh R antagonists with improved selectivity might trigger novel strategies for the intervention and prevention of lung cancer. Here we review the genetic risk factors for lung cancer in the n ACh R gene cluster, the roles of nicotine receptors, and the molecular mechanisms of acetylcholine receptor pathways to lead to more opportunities for intervention and prevention of lung cancer.