Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor...Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.展开更多
The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular...The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular membrane of lung tissue were measured with fluorescent polarization and high performance liquid chromatography respectively. The findings were as follows:1- Four hours after endotoxin injection, there was a 47% decrease of the maximal binding capacity of fyARsas compared with the control.2. Endotoxin was able to decrease the lipid fluidity and phospholipid content of the pulmonary cellular membrane markedly and at the same time. There was an elevated activity of phospholipase A2 in the pulmonary tissueThese findings suggest that the decrease of the binding capacity of &ARs results in a decrease of the PAR mediated functions, which plays a ro1e in the pathogensis of endotoxin-induced acute lung injury and the activation of phospholipase A2 which is an important factor to reduce the phospholipid content of cell membrane and subsequently to decrease its lipid fluidity, can result in a reduction of the lateral diffusion and rotatory movement of β-ARs and to decrease the chances of β-ARs to bind with the ligands.展开更多
Objective:To investigate Petroselinum crispum Latifolum(parsley) for treating stomach and intestinal disorders in Iran.Methods:An 80%ethanol extract was prepared from parsley seeds, and its antispasmodic activity asse...Objective:To investigate Petroselinum crispum Latifolum(parsley) for treating stomach and intestinal disorders in Iran.Methods:An 80%ethanol extract was prepared from parsley seeds, and its antispasmodic activity assessed by measuring contractions of isolated ilea induced by 60 mM potassium chloride(KG).A piece of ileum from an adult male Wistar rat was dissected and mounted in an organ bath containing Tyrode’s solution,and ileum contractions were recorded by an isotonic transducer under one gram resting tension.The effect of parsley extract was measured in the presence of two antagonists’ of a - and(5-adrenoceptors.Results:These experiments showed that parsley extract inhibited the response to 60 mM KC1 in a concentration-dependent manner(P【0.01,n=7).The spasmolytic effect of parsley extract was unaffected by 1μM phentolamine or 1μM propranolol.Conclusions:This study shows that parsley seed extract is a relaxant of isolated rat ileum and the relaxation effect of extract does not involved adrenergic receptors.展开更多
To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal...To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.RESULTSB2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.CONCLUSIONB2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.展开更多
Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patien...Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.展开更多
Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represent...Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.展开更多
Beta-adrenergic receptors in the brain are involved in modulating cerebral blood flow (CBF) and cerebral energy metabolism (CEM). Because of the difficult availability of brain tissue samples, investigation of the rel...Beta-adrenergic receptors in the brain are involved in modulating cerebral blood flow (CBF) and cerebral energy metabolism (CEM). Because of the difficult availability of brain tissue samples, investigation of the relevant beta-receptor of brain is limited. In the present study, the density of beta-receptors in brain tissues and in circulating lymphocytes was measured by the method of radio-ligand receptor binding (RLBA), in brain injury or brain tumor and a correlation analysis was performed. Our results show that there is linear correlation between the beta-receptors in brain tissue and in peripheral blood lymphocytes (r= 0. 811 , P<0. 01) in cases of increased permeability of bloodbrain barrier during brain injury or brain tumor.展开更多
Changes of pulmonary α1-and βadrenergic receptors (α1- ARs and β-ARs) after endotoxin-induced lung injury were dynamically observed with radioligand binding assay and the pulmonary rnicrovascular permeability and ...Changes of pulmonary α1-and βadrenergic receptors (α1- ARs and β-ARs) after endotoxin-induced lung injury were dynamically observed with radioligand binding assay and the pulmonary rnicrovascular permeability and histopathology were also studied in rats to investigate the relationship between changes of pu1monary ARs and acute lung injury. It was found that the contents of both α1-ARs and β-ARs were significantly decreased after endotoxin-induced acute lung injury. On the basis of these findings, the authors inferred that the down regulation of β-ARs might be one of the factors to increase pulmonary microvascular permeability and that of α1-ARs seems to be a protective reaction. This inference might serve as the theoretical basis to treat pulmonary edema with α1-antagonists and β-agonists clinically.展开更多
The objective of this study was to determine if the addition of zinc (Zn) in combination with zilpaterol HCL (ZH) affected the interaction of ZH with the beta2-adrenergic receptor (<span style="white-space:now...The objective of this study was to determine if the addition of zinc (Zn) in combination with zilpaterol HCL (ZH) affected the interaction of ZH with the beta2-adrenergic receptor (<span style="white-space:nowrap;"><i></i></span><i>β<span style="white-space:nowrap;"></span></i>-AR) by altering cAMP production, gene expression, and protein abundance in cultured skeletal muscle cells. Cultures of muscle bovine satellite cells were established and treated at 120 h with: 1) 0 μM Zn/zilpaterol hydrochloride (ZH;<strong>CON</strong>);2) 0 μM Zn/10 μM ZH (<strong>ZH</strong>);3) 1 μM Zn from Zn chloride/0 μM ZH (<strong>Zn</strong>);4) 1 μM Zn from Zn chloride/10 μM ZH (<strong>ZN/ZH</strong>) in differentiation media for an additional 0, 6, 24, 48 and 96 h. Protein and mRNA were isolated and quantified at 24 and 96 h, and cAMP was measured at 0, 6, 24, 48 and 96 h. At 0, 24, 48 and 96 h, no differences (<i><span style="white-space:normal;">P</span></i> > 0.05) were detected in cAMP production. At 6 h, Zn cells had the greatest concentration of cAMP (<span style="white-space:nowrap;"><i></i></span><i>P<span style="white-space:nowrap;"></span></i> < 0.05) compared to ZH treatments. No differences (<i><span style="white-space:normal;">P</span></i> > 0.05) were detected in mRNA abundance at 24 h. At 96 h, 0 μM Zn/10 μM ZH cells had an increased abundance of myosin heavy chain (MHC)-I mRNA (<i><span style="white-space:normal;">P</span></i> < 0.05) compared to CON. Furthermore, ZH had a greater abundance of MHC-IIX mRNA (<i><span style="white-space:normal;">P</span></i> < 0.05) and a tendency for a greater abundance of IGF-1 mRNA (<span style="white-space:normal;"><i></i></span><i><span style="white-space:normal;">P</span><span style="white-space:normal;"></span></i> < 0.15) compared to CON and ZN/ZH. No differences (<i><span style="white-space:normal;">P</span></i> > 0.05) were detected in the protein abundance of <i><span style="white-space:normal;">β</span></i>1AR and the <i><span style="white-space:normal;">β</span></i>2AR. These results indicated Zn and ZH in combination did not have an additive effect on<em> β</em>2-AR function as indicated by cAMP concentrations.展开更多
Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcr...Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation(mitochondrial and peroxisomal)and microsomal omega-oxidation, being markedly decreased by high-fat(HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs.展开更多
In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) innormal and experimental allergic asthmatic guinea pigs was determined using autoradiograph-ic method. The results showed that t...In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) innormal and experimental allergic asthmatic guinea pigs was determined using autoradiograph-ic method. The results showed that the distribution of beta-receptors in the lung sections waswidespread. There was a significant decrease of beta-receptor density in several tissue struc-tures of asthmatic guinea pig lungs compared with the controls, a 23.73% decrease in beta-recep-tor binding sites in bronchiolar smooth muscles and a 18.65% decrease in bronchial smoothmuscles; a 23 .53%. a 14.23% and a 17. 16% decrease in bronchiolar epithelium, in bronchialepithelium and in alveolar epithelium respectively. The results indicated that the beta-recep-tor decrease in smooth muscles in experimental asthmatic guinea pig lungs might be one ofthe important factors which made the tension of smooth muscles increase. The relationshipbetween the beta-receptor decrease of other sites and bronchial asthma needs to be studiedfurther.展开更多
Catecholamines such as adrenaline, norepinephrine and isoproterenol regulate a wide variety of physiological responses via their specific binding to adrenergic receptors located in the plasma membrane. Adrenergic rece...Catecholamines such as adrenaline, norepinephrine and isoproterenol regulate a wide variety of physiological responses via their specific binding to adrenergic receptors located in the plasma membrane. Adrenergic receptors have been divided into two major types, α and β. Binding of ligands to β-adrenergic receptors (β-AR) first triggers the activation of stimulatory GTP-binding protein (Gs). The activated Gs then interacts展开更多
Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the ...Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 (ICI), on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic (TG) mice treated with ICI (AD-TG/ICI) was significantly poorer compared with NaCl-treated AD-TG mice (AD-TG/NaCl), suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.展开更多
BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is he...BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE: To analyze the association between the polymorphism of beta1 adrenergic receptor (β1-AR) gene G1165C (Arg389Gly), an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN : A cross-sectional study SETTINGS: Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS: The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure: ① Normal blood pressure group (n=117): systolic blood pressure (SBP) 〈 140 mm Hg (1 mm Hg =0.133 kPa), diastolic blood pressure (DBP) 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group (n=122): including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS : The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood (5 mL) was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C (Gly389Arg) genotype were detected with the Sequenom system. Polymerase chain reaction (PCR) experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio (OR) and 95% confidence interval (CO were calculated. MAIN OUTCOME MEASURES: The distributions of β1-AR Gl165C (Gly389Arg) genotypes and alleles were observed. RESULTS: A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C (Gly389Arg) genotypes and allele distnbutions: In Mongolian population, the frequencies of CC and GG+GC genotypes at β1-AR G1165C (Gly389Arg) site in the essential hypertension group (72%, 28%) were not significantly different from those in the normal blood pressure group (67%, 33%) (xz=0.841, P=-0.359; OR 0.773, 95%Cl: 0.445-1.342); The frequencies of C and G alleles also had no significant differences between the essential hypertension group (85%, 15%) and the normal blood pressure group (82%, 18%) (x^2=1.136, P=-0.287; OR: 0.769, 95%Cl: 0.747-1.248). ②The frequencies of CC and GG+GC genotypes at β1-AR G1165C (Gly389Arg) site had no significant differences between the patients with simple high SBP (71%, 29%) and the normal blood pressure group (x^2=0.250, P=-0.617; OR: 0.833, 95%C/: 0.408-1.703); The frequencies of C and G alleles were not significantly different between the patients with simple high SBP (86%, 14%) and the normal blood pressure group (x^2=0.670, P=-0.413; OR 0.766, 95%Cl: 0.404-1.453). CONCLUSION: In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C (Gly389Arg) have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension (including simple SBP increase), which suggests that G1165C (Glu389Asp) site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.展开更多
Chinese visceral manifestation theory states that lung dominates qi,regulates breathing,and governs Xuanfa(dispersing)and Sujiang(descending).Clarifying this theory with modern physiological and pathological knowl...Chinese visceral manifestation theory states that lung dominates qi,regulates breathing,and governs Xuanfa(dispersing)and Sujiang(descending).Clarifying this theory with modern physiological and pathological knowledge has been considered as an important part of complementary and alternative medicine therapy.Previous studies found that most Xuanfa drugs contained pharmacodynamic ingredients related to adrenergic receptors(ARs)signal transduction.The association of Xuanfa,with the control of breath movement,nutrient transfer,spreading heat to regulate temperature,and helping the heart control blood circulation,coincides with the physiological function of organs dominated by ARs-regulated sympathetic postganglionic fibers.Therefore,we hypothesize that Xuanfa is closely related to ARs-regulated signal transduction.By modern biological knowledge,we tried to evaluate and expound the correlation between the molecular mechanisms of modern physiology or pathology and Xuanfa or Sujiang theory.Ultimately,the research and development of modern drugs should fully expect the guidance from Chinese visceral manifestation theory,and the application of this principle will guide the prevention and clinical treatment of a variety of refractory diseases caused by a change in environment,climate,or lifestyle.展开更多
It is well known that, under physiological conditions, the cytosolic free Ca<sup>2+</sup> in most cells is around 10<sup>-7</sup>—10<sup>-6</sup> mol/L, whereas the extracellular C...It is well known that, under physiological conditions, the cytosolic free Ca<sup>2+</sup> in most cells is around 10<sup>-7</sup>—10<sup>-6</sup> mol/L, whereas the extracellular Ca<sup>2+</sup> concentration is about 10<sup>-3</sup> mol/L. This results in a 1 000—10 000-fold transmembrane Ca<sup>2+</sup> gradient. The maintenance of such a concentration gradient has been proved to be of vital importance in cell function. Although a transmembrance Ca<sup>2+</sup> gradient exists across the plasma membrance, little attention has展开更多
Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were ...Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces, which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.展开更多
FK506 binding protein 12.6 (FKBP12.6) is the protein in the ryanodine receptor complex, but its function is controversial in different reported work. Some conclude that FKBP12.
文摘Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.
文摘The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular membrane of lung tissue were measured with fluorescent polarization and high performance liquid chromatography respectively. The findings were as follows:1- Four hours after endotoxin injection, there was a 47% decrease of the maximal binding capacity of fyARsas compared with the control.2. Endotoxin was able to decrease the lipid fluidity and phospholipid content of the pulmonary cellular membrane markedly and at the same time. There was an elevated activity of phospholipase A2 in the pulmonary tissueThese findings suggest that the decrease of the binding capacity of &ARs results in a decrease of the PAR mediated functions, which plays a ro1e in the pathogensis of endotoxin-induced acute lung injury and the activation of phospholipase A2 which is an important factor to reduce the phospholipid content of cell membrane and subsequently to decrease its lipid fluidity, can result in a reduction of the lateral diffusion and rotatory movement of β-ARs and to decrease the chances of β-ARs to bind with the ligands.
基金supported by the Department of Biology,Shahid Chamran University,Ahwaz,Iran
文摘Objective:To investigate Petroselinum crispum Latifolum(parsley) for treating stomach and intestinal disorders in Iran.Methods:An 80%ethanol extract was prepared from parsley seeds, and its antispasmodic activity assessed by measuring contractions of isolated ilea induced by 60 mM potassium chloride(KG).A piece of ileum from an adult male Wistar rat was dissected and mounted in an organ bath containing Tyrode’s solution,and ileum contractions were recorded by an isotonic transducer under one gram resting tension.The effect of parsley extract was measured in the presence of two antagonists’ of a - and(5-adrenoceptors.Results:These experiments showed that parsley extract inhibited the response to 60 mM KC1 in a concentration-dependent manner(P【0.01,n=7).The spasmolytic effect of parsley extract was unaffected by 1μM phentolamine or 1μM propranolol.Conclusions:This study shows that parsley seed extract is a relaxant of isolated rat ileum and the relaxation effect of extract does not involved adrenergic receptors.
基金Supported by the Romanian National Authority for Scientific Research and Innovation,CNCS-UEFISCDI,project No.PN-IIRU-TE-2014-4-0582,contract No.160/01.10.2015
文摘To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.RESULTSB2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.CONCLUSIONB2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.
基金the Beijing Natural Science Foundation (No. 7174306)。
文摘Objective To determine the possible association of anti-β1-adrenergic receptors(anti-β1-AR), anti-β2-AR and anti-α1-AR with carvedilol treatment in patients with heart failure(HF). Methods A total of 267 HF patients were prospectively enrolled. Blood samples were measured by an enzyme-linked immunosorbent assay. All of the patients received carvedilol for their HF. Each patient was followed up for six months and their cardiac function was measured. Results The final analysis encompassed 137 patients comprising 65 patients with three autoantibodies(positive group) and 72 patients without all three autoantibodies but with one or two autoantibodies(negative group). The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR, and anti-α1-AR were significantly lower in the group without all three autoantibodies after six months of carvedilol treatment(all P < 0.01;from 100% to 57%, 50%, and 49%, respectively;and from 1: 118, 1: 138, and 1: 130 to 1: 72, 1: 61, and 1: 67, respectively). Furthermore, 28 patients in the positive group demonstrated complete ablation of autoantibodies. In addition, left ventricular remodelling and function was significantly improved by the use of carvedilol combined with the standard treatment regime for six months in the positive group(P < 0.01) when compared to the negative group(P < 0.05). Conclusions Carvedilol treatment significantly decreases frequency and geometric mean titer in patients with all three autoantibodies, even up to complete ablation, and significantly improved cardiac function and remodelling. The effect of carvedilol is probably correlated to the presence of all three autoantibodies.
基金This work was partially supported by the pharmaceutical company Astra Zeneca and by Fondazione Generali.
文摘Positive modulation of adult hippocampal neurogenesis may contribute to the therapeutic effects of clinically relevant antidepressant drugs,including atypical antipsychotics.Quetiapine,an antipsychotic which represents a therapeutic option in patients who are resistant to classical antidepressants,promotes adult hippocampal neurogenesis in preclinical studies.Norquetiapine,the key active metabolite of quetiapine in humans,has a distinctive receptor profile than the parent compound.The drug is indeed a high affinity norepinephrine transporter inhibitor and such activity has been proposed to contribute to its antidepressant effect.At present,no information is available on the effects of norquetiapine on adult neurogenesis.We extensively investigated the activity of quetiapine and norquetiapine on adult murine neural stem/progenitor cells and their progeny.Additionally,selective antagonists for β_(2)/α_(2) adrenergic receptors allowed us to evaluate if these receptors could mediate quetiapine and norquetiapine effects.We demonstrated that both drugs elicit in vitro proneurogenic effects but also that norquetiapine had distinctive properties which may depend on its ability to inhibit norepinephrine transporter and involve β_(2)/α_(2) adrenergic receptors.Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committees(IACUC)at University of Piemonte Orientale,Italy(approval No.1033/2015PR)on September 29,2015.
文摘Beta-adrenergic receptors in the brain are involved in modulating cerebral blood flow (CBF) and cerebral energy metabolism (CEM). Because of the difficult availability of brain tissue samples, investigation of the relevant beta-receptor of brain is limited. In the present study, the density of beta-receptors in brain tissues and in circulating lymphocytes was measured by the method of radio-ligand receptor binding (RLBA), in brain injury or brain tumor and a correlation analysis was performed. Our results show that there is linear correlation between the beta-receptors in brain tissue and in peripheral blood lymphocytes (r= 0. 811 , P<0. 01) in cases of increased permeability of bloodbrain barrier during brain injury or brain tumor.
文摘Changes of pulmonary α1-and βadrenergic receptors (α1- ARs and β-ARs) after endotoxin-induced lung injury were dynamically observed with radioligand binding assay and the pulmonary rnicrovascular permeability and histopathology were also studied in rats to investigate the relationship between changes of pu1monary ARs and acute lung injury. It was found that the contents of both α1-ARs and β-ARs were significantly decreased after endotoxin-induced acute lung injury. On the basis of these findings, the authors inferred that the down regulation of β-ARs might be one of the factors to increase pulmonary microvascular permeability and that of α1-ARs seems to be a protective reaction. This inference might serve as the theoretical basis to treat pulmonary edema with α1-antagonists and β-agonists clinically.
文摘The objective of this study was to determine if the addition of zinc (Zn) in combination with zilpaterol HCL (ZH) affected the interaction of ZH with the beta2-adrenergic receptor (<span style="white-space:nowrap;"><i></i></span><i>β<span style="white-space:nowrap;"></span></i>-AR) by altering cAMP production, gene expression, and protein abundance in cultured skeletal muscle cells. Cultures of muscle bovine satellite cells were established and treated at 120 h with: 1) 0 μM Zn/zilpaterol hydrochloride (ZH;<strong>CON</strong>);2) 0 μM Zn/10 μM ZH (<strong>ZH</strong>);3) 1 μM Zn from Zn chloride/0 μM ZH (<strong>Zn</strong>);4) 1 μM Zn from Zn chloride/10 μM ZH (<strong>ZN/ZH</strong>) in differentiation media for an additional 0, 6, 24, 48 and 96 h. Protein and mRNA were isolated and quantified at 24 and 96 h, and cAMP was measured at 0, 6, 24, 48 and 96 h. At 0, 24, 48 and 96 h, no differences (<i><span style="white-space:normal;">P</span></i> > 0.05) were detected in cAMP production. At 6 h, Zn cells had the greatest concentration of cAMP (<span style="white-space:nowrap;"><i></i></span><i>P<span style="white-space:nowrap;"></span></i> < 0.05) compared to ZH treatments. No differences (<i><span style="white-space:normal;">P</span></i> > 0.05) were detected in mRNA abundance at 24 h. At 96 h, 0 μM Zn/10 μM ZH cells had an increased abundance of myosin heavy chain (MHC)-I mRNA (<i><span style="white-space:normal;">P</span></i> < 0.05) compared to CON. Furthermore, ZH had a greater abundance of MHC-IIX mRNA (<i><span style="white-space:normal;">P</span></i> < 0.05) and a tendency for a greater abundance of IGF-1 mRNA (<span style="white-space:normal;"><i></i></span><i><span style="white-space:normal;">P</span><span style="white-space:normal;"></span></i> < 0.15) compared to CON and ZN/ZH. No differences (<i><span style="white-space:normal;">P</span></i> > 0.05) were detected in the protein abundance of <i><span style="white-space:normal;">β</span></i>1AR and the <i><span style="white-space:normal;">β</span></i>2AR. These results indicated Zn and ZH in combination did not have an additive effect on<em> β</em>2-AR function as indicated by cAMP concentrations.
文摘Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation(mitochondrial and peroxisomal)and microsomal omega-oxidation, being markedly decreased by high-fat(HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs.
文摘In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) innormal and experimental allergic asthmatic guinea pigs was determined using autoradiograph-ic method. The results showed that the distribution of beta-receptors in the lung sections waswidespread. There was a significant decrease of beta-receptor density in several tissue struc-tures of asthmatic guinea pig lungs compared with the controls, a 23.73% decrease in beta-recep-tor binding sites in bronchiolar smooth muscles and a 18.65% decrease in bronchial smoothmuscles; a 23 .53%. a 14.23% and a 17. 16% decrease in bronchiolar epithelium, in bronchialepithelium and in alveolar epithelium respectively. The results indicated that the beta-recep-tor decrease in smooth muscles in experimental asthmatic guinea pig lungs might be one ofthe important factors which made the tension of smooth muscles increase. The relationshipbetween the beta-receptor decrease of other sites and bronchial asthma needs to be studiedfurther.
文摘Catecholamines such as adrenaline, norepinephrine and isoproterenol regulate a wide variety of physiological responses via their specific binding to adrenergic receptors located in the plasma membrane. Adrenergic receptors have been divided into two major types, α and β. Binding of ligands to β-adrenergic receptors (β-AR) first triggers the activation of stimulatory GTP-binding protein (Gs). The activated Gs then interacts
基金supported by the Key Laboratory of Brain Disease Bioinformation of Jiangsu Province of China,No.Jsbl1202
文摘Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer's disease (AD), although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 (ICI), on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic (TG) mice treated with ICI (AD-TG/ICI) was significantly poorer compared with NaCl-treated AD-TG mice (AD-TG/NaCl), suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.
基金a grant from theGreat Program of Inner Mongo-lia Medical College, No.NY2004ZD006
文摘BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE: To analyze the association between the polymorphism of beta1 adrenergic receptor (β1-AR) gene G1165C (Arg389Gly), an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN : A cross-sectional study SETTINGS: Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS: The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure: ① Normal blood pressure group (n=117): systolic blood pressure (SBP) 〈 140 mm Hg (1 mm Hg =0.133 kPa), diastolic blood pressure (DBP) 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group (n=122): including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS : The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood (5 mL) was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C (Gly389Arg) genotype were detected with the Sequenom system. Polymerase chain reaction (PCR) experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio (OR) and 95% confidence interval (CO were calculated. MAIN OUTCOME MEASURES: The distributions of β1-AR Gl165C (Gly389Arg) genotypes and alleles were observed. RESULTS: A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C (Gly389Arg) genotypes and allele distnbutions: In Mongolian population, the frequencies of CC and GG+GC genotypes at β1-AR G1165C (Gly389Arg) site in the essential hypertension group (72%, 28%) were not significantly different from those in the normal blood pressure group (67%, 33%) (xz=0.841, P=-0.359; OR 0.773, 95%Cl: 0.445-1.342); The frequencies of C and G alleles also had no significant differences between the essential hypertension group (85%, 15%) and the normal blood pressure group (82%, 18%) (x^2=1.136, P=-0.287; OR: 0.769, 95%Cl: 0.747-1.248). ②The frequencies of CC and GG+GC genotypes at β1-AR G1165C (Gly389Arg) site had no significant differences between the patients with simple high SBP (71%, 29%) and the normal blood pressure group (x^2=0.250, P=-0.617; OR: 0.833, 95%C/: 0.408-1.703); The frequencies of C and G alleles were not significantly different between the patients with simple high SBP (86%, 14%) and the normal blood pressure group (x^2=0.670, P=-0.413; OR 0.766, 95%Cl: 0.404-1.453). CONCLUSION: In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C (Gly389Arg) have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension (including simple SBP increase), which suggests that G1165C (Glu389Asp) site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.
基金National Natural Science Foundation of China(81173638,81373506)Specialized Research Fund for the Doctoral Program of Higher Education(20120031110042)
文摘Chinese visceral manifestation theory states that lung dominates qi,regulates breathing,and governs Xuanfa(dispersing)and Sujiang(descending).Clarifying this theory with modern physiological and pathological knowledge has been considered as an important part of complementary and alternative medicine therapy.Previous studies found that most Xuanfa drugs contained pharmacodynamic ingredients related to adrenergic receptors(ARs)signal transduction.The association of Xuanfa,with the control of breath movement,nutrient transfer,spreading heat to regulate temperature,and helping the heart control blood circulation,coincides with the physiological function of organs dominated by ARs-regulated sympathetic postganglionic fibers.Therefore,we hypothesize that Xuanfa is closely related to ARs-regulated signal transduction.By modern biological knowledge,we tried to evaluate and expound the correlation between the molecular mechanisms of modern physiology or pathology and Xuanfa or Sujiang theory.Ultimately,the research and development of modern drugs should fully expect the guidance from Chinese visceral manifestation theory,and the application of this principle will guide the prevention and clinical treatment of a variety of refractory diseases caused by a change in environment,climate,or lifestyle.
基金National Natural Science Foundation of ChinaChinese Academy of Sciences.
文摘It is well known that, under physiological conditions, the cytosolic free Ca<sup>2+</sup> in most cells is around 10<sup>-7</sup>—10<sup>-6</sup> mol/L, whereas the extracellular Ca<sup>2+</sup> concentration is about 10<sup>-3</sup> mol/L. This results in a 1 000—10 000-fold transmembrane Ca<sup>2+</sup> gradient. The maintenance of such a concentration gradient has been proved to be of vital importance in cell function. Although a transmembrance Ca<sup>2+</sup> gradient exists across the plasma membrance, little attention has
文摘Summary: The experimental results showed that the level of CAMP, the ratio of cAPM to cGMP, IL-2R expression and IL-2 production in vitro in lymphocytes immediate and 2 weeks after car- diopulmonary bypass (CPB) were significantly lower than those before anesthetics in the patients undergoing cardiac surgery with CPB. These findings suggested that CPB could cause serious damage to adrenergic beta receptor-adenylate cyclase system on circulating lymphocytes surfaces, which might be one of the mechanisms resulting in immunosuppression after open heart surgery with CPB.
文摘FK506 binding protein 12.6 (FKBP12.6) is the protein in the ryanodine receptor complex, but its function is controversial in different reported work. Some conclude that FKBP12.