Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease

Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.

Effects of 5-hydroxytryptamine Receptor on the Reaction of the Lower Esophageal Sphincter Under the Electrical Field Stimulation

In the first and second parts of this study,5-hydroxytryptamine(5HT)receptors,including 5-HT3 and 5-HT4 with the highest expression level,were found in clasp and sling fibres of the lower esophageal sphincter(LES).Specific 5-HT3 and 5-HT4 receptor agonists can induce the contraction effect of clasp and sling fibres of the LES while specific 5-HT7 receptor agonists showed no effects.In the study of this part,the in-vitro muscle tension measurement technology and EFS methods were used to detect the effect of the selective 5-HT receptor antagonist on the clasp and sling fibres of the in-vitro LES under the electrical field stimulation(EFS),and further to ensure the effect of 5-HT receptor in the LES neuroregulatory pathway,and deeply explore the effect of 5-HT receptor in the systolic and diastolic function regulation of the LES.

Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT_(3)R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT_(3)Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT_(3)Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and theγ-aminobutyric acid(GABA)“disinhibition”mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT_(3)R-induced GABA“disinhibition”mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT_(2)R-mediated regulation of anxiety reactions are also activated by 5-HT_(3)R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT_(3)Rs.However,given the circuit specific modulation of 5-HT_(3)Rs on emotion,systemic use of 5-HT_(3)R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT_(3)R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.

Distribution of serotonin 5-HT_(2A) and 5-HT_7 receptors in the Onuf’s nucleus of the rat spinal cord

BACKGROUND：Motoneurons from the Onuf’s nucleus of the spinal cord, which innervate the striated muscle of the pelvic floor, play an important role in erection, ejaculation, and urine control. Serotonin （5-hydroxytryptamine, 5-HT） regulates motoneuron activity from the Onuf’s nucleus of the spinal cord. However, few studies exist that describe 5-HT receptor distribution in the Onuf’s nucleus. In addition, the nature of the effects of 5-HT receptor on the innervating striated muscle of the pelvic floor is controversial. OBJECTIVE： To investigate the distribution of serotonin 5-HT2A and 5-HT7 receptors in motoneurons of Onuf’s nucleus in the spinal cord of male rats, and to analyze the relationship of 5-HT2A and 5-HT7 receptor to central modulation of urogenital function. DESIGN, TIME AND SETTING： The neural morphology experiment was performed at the Ultramicro-structure Laboratory of Reproductive Medicine, Basic Medical College, Chongqing Medical University, China from April to December 2007. MATERIALS： Ten adult, Sprague Dawley rats （eight males and two females） were randomly divided into gender control group （n = 4, 50% male and 50% female） and a retrograde tracing group （n = 6, 100% male） Recombinant pseudorabies virus （PRV-152） was provided by Professor LW Enquist from Princeton University, USA. Rabbit anti-5-HT2A and 5-HT7 receptor antibodies were purchased from Diasorin, France. METHODS： In the gender control group, the spinal L5-6 segments were harvested, sliced, and then incubate antibodies specific against 5-HT2A or 5-HT7 receptors for immunohistochemical staining. In the retrograde tracing group, PRV-152 was separately injected into the right ischiocavernosus （ischiocavernosus subgroup, n = 3） and the right external urethral sphincter （external urethral sphincter subgroup, n = 3）. Four days after injection, L5-6 segments were harvested, sliced, and incubated with antibodies specific against 5-HT2A or 5-HT7 receptors for double-labeling immunofluorescence staining. MAIN OUTCOME MEASURES： Distribution analysis of 5-HT2A and 5-HT7 receptors in Onuf’s nucleus utilizing optical or laser confocal microscopy. RESULTS： 5-HT2A receptor immunoreactivity was revealed primarily in the medial region of the dorsolateral nucleus of Onuf’s nucleus. 5-HT7 receptor expression was observed in the lateral part of the dorso-lateral nucleus. 5-HT2A and 5-HT7 receptor expressions in the Onuf’s nucleus were significantly greater in male rats, compared to female rats. Double-labeling immunofluorescence demonstrated that 5-HT2A recepto were distributed primarily in the surrounding motoneurons innervating the ischiocavernosus, and 5-HT7 receptors were primarily expressed in motoneurons innervating the external urethral sphincter. CONCLUSION： Motoneurons innervating the ischiocavernosus and external urethral sphincter are located primarily in the medial and lateral region of the dorsolateral nucleus of L5-6 segments. The 5-HT2A receptor-innervating ischiocavernosus may be preferentially involved in the regulation of sexual reflex, and the 5-HT7 receptor-innervating external urethral sphincter may mainly join in regulating micturition reflex.

Predominant mucosal expression of 5-HT_(4(+h)) receptor splice variants in pig stomach and colon

AIM: To investigate cellular 5-HT4(-h/+h) receptor distribution, particularly in the epithelial layer, by laser mi-crodissection and polymerase chain reaction (PCR) in porcine gastrointestinal (GI) tissues. METHODS: A stepwise approach was used to evaluate RNA quality and to study cell-specific 5-HT4 receptor mRNA expression in the porcine gastric fundus and colon descendens. After freezing, staining and laser microdissection and pressure catapulting (LMPC), RNA quality was evaluated by the Experion automated electrophoresis system. 5-HT4 receptor and glyceral-dehyde-3-phosphate dehydrogenase (GAPDH) expressions were examined by endpoint reverse transcription (RT)-PCR in mucosal and muscle-myenteric plexus (MMP) tissue fractions, in mucosal and MMP parts of hematoxylin and eosin (HE) stained tissue sections andin microdissected patches of the epithelial and circular smooth muscle cell layer in these sections. Pig gastric fundus tissue sections were also stained immunohisto-chemically (IHC) for enterochromaffin cells (EC cells; MAB352); these cells were isolated by LMPC and examined by endpoint RT-PCR. RESULTS: After HE staining, the epithelial and circular smooth muscle cell layer of pig colon descendens and the epithelial cell layer of gastric fundus were identified morphologically and isolated by LMPC. EC cells of pig gastric fundus were successfully stained by IHC and isolated by LMPC. Freezing, HE and IHC staining, and LMPC had no influence on RNA quality. 5-HT4 recep-tor and GAPDH mRNA expressions were detected in mucosa and MMP tissue fractions, and in mucosal and MMP parts of HE stained tissue sections of pig colon descendens and gastric fundus. In the mucosa tissue fractions of both GI regions, the expression of h-exon containing receptor [5-HT4(+h) receptor] mRNA was significantly higher (P<0.01) compared to 5-HT4(-h) re-ceptor expression, and a similar trend was obtained in the mucosal part of HE stained tissue sections. Large microdissected patches of the epithelial and circular smooth muscle cell layer of pig colon descendens and of the epithelial cell layer of pig gastric fundus, also showed 5-HT4 receptor and GAPDH mRNA expression. No 5-HT4 receptor mRNA expression was detected in gastric LMPC-isolated EC cells from IHC stained tissues, which cells were positive for GAPDH. CONCLUSION: Porcine GI mucosa predominantly expresses 5-HT4(+h) receptor splice variants, suggesting their contribution to the 5-HT4 receptor-mediated mu-cosal effects of 5-HT.

UFLC‑PDA‑MS/MS Profling of Seven Uncaria Species Integrated with Melatonin/5‑Hydroxytryptamine Receptors Agonistic Assay

Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.

The role of 5-HT_7 Receptor in the pathogenesis of IBS

Objective：To investigate the role of 5-HT7 receptor in the pathogenesis of irritable bowel syndrome（IBS）. Methods：Rat model of D-IBS was established by intracolonic instillation of acetic acid and restraint stress; Rat model of C-IBS was established by stomach irrigated with 0-4℃ cool water daily for 14 d. The content and distribution of 5-HT7 receptor at the brain and bowel was examined by immunohistochemistry and the expression of 5-HT7 receptor mRNA was detected by fluorescence quantitative RT-PCR（Real-time PCR）. Results：Immunocytochemistry result showed the 5-HT7 rceptor positive staining at hippocampus and hypothalamus of both C-IBS and D-IBS group was stronger than that of control group（P 〈 0.01）. The 5-HT7R expression at ileum, proximate colon, distal colon of C-IBS group was significantly stronger than that of control group（P 〈 0.05）. Realtime-PCR analysis results showed the expression level of 5-HT7 receptor at hippocampus and hypothalamus of both C-IBS and D-IBS group was increased than that of control group（P〈 0.05）. At proximal and distal colon of C-IBS group, the 5-HT7 receptor mRNA expression was increased compared with control group（P〈 0.05）. Conclusion：The up-regulated expression of 5-HT7 receptor at brain and colon may play an important role in the pathogenesis of C-IBS.

Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors:a systematic review

Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to insomnia,in order to develop innovative therapies and new compounds.Recently,increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia.Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain.In this review,the role of 5-hydroxytryptamine(5-HT)in insomnia development is summarized,while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes,in order to provide reference for subsequent research.

N-(2-(2-Methoxyphenylthio)benzyl)-2-aryloxyethylamines:Synthesis and evaluation for dual 5-HT_(1A)/SSRI activities

The design, synthesis and biological evaluation of N-（2-（2-methoxyphenylthio） benzyl）-2-aryloxyethyl amines with dual 5-HT1A/SSR/activities are reported. Compound 8e displays the best dual activities and is a promising lead compound for further SAR studies.

1-[2-(2-Methoxyphenylthio) benzyl]-4-arylpiperazines derivatives:Synthesis and evaluation for dual 5-HT_(1A)/SSRI activities

A series of 1-[2-（2-methoxyphenylthio） benzyl]-4-arylpiperazines derivatives was designed and synthesized based on 5-HT1A/ SSRI drugs design strategies. The synthesized compounds were evaluated for their dual 5-HT1A/5-HTT activities. 2007 Ai Jun Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Bioassay-guided isolation of saikosaponins with agonistic activity on 5-hydroxytryptamine 2C receptor from Bupleurum chinense and their potential use for the treatment of obesity

5-Hydroxytryptamine 2C(5-HT2C) receptor is one of the major targets of anti-obesity agents, due to its role in regulation of appetite. In the present study, the 70% EtO H extract of the roots of Bupleurum chinense was revealed to have agonistic activity on 5-HT2 C receptor, and the subsequent bioassay-guided isolation led to identification of several saikosaponins as the active constituents with 5-HT2 C receptor agonistic activity in vitro and anti-obesity activity in vivo. The new compound, 22-oxosaikosaponin d(1), was determined by extensive spectroscopic analyses(HR-ESI-MS, IR, and 1D and 2D NMR). The primary structure-activity relationship study suggested that the intramolecular ether bond between C-13 and C-28 and the number of sugars at C-3 position were closely related to the 5-HT2 C receptor agonistic activity. Saikosaponin a(3), the main saponin in B. chinense, showed obviously agonistic activity on 5-HT2 C receptor with an EC50 value of 21.08 ± 0.33 μmol×L^(–1) in vitro and could reduce food intake by 39.1% and 69.2%, and weight gain by 13.6% and 16.4%, respectively, at 3.0 and 6.0 mg×kg^(–1) in vivo. This investigation provided valuable information for the potential use of B. chinense as anti-obesity agent.

Domesticated HERV-W env contributes to the activation of the small conductance Ca^(2+)-activated K^(+)type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia

The human endogenous retroviruses type W family envelope(HERV-W env)gene is located on chromosome 7q21-22.Our previous studies show that HERV-W env is elevated in schizophrenia and HERV-W env can increase cal-cium influx.Additionally,the 5-HTergie system and particularly 5-hydroxytryptamine(5-HT)receptors play a prominent role in the pathogenesis and treatment of schizophrenia.5-hydroxytryptamine receptor 4(5-HT4R)agonist can block calcium channels.However,the underlying relationship between HERV-W env and 5-HT4R in the etiology of schizophrenia has not been revealed.Here,we used enzyme-linked immunosorbent assay to detect the concentration of HERV-W env and 5-HT4R in the plasma of patients with schizophrenia and we found that there were decreased levels of 5-HT4R and a negative correlation between 5-HT4R and HERV-W env in schizophrenia.Overexpression of HERV-W env decreased the transcription and protein levels of 5-HT4R but increased small conductance Ca^(2+)-activated K^(+)type 2 channels(SK2)expression levels.Further studies revealed that HERV-w env could interact with 5-HT4R.Additionally,luciferase assay showed that an essential region(-364 to-176 from the transcription start site)in the SK2 promoter was required for HERV-W env-induced SK2 expression.Importantly,5-HT4R participated in the regulation of SK2 expression and promoter activity.Electrophysiological recordings suggested that HERV-Wenv could increase SK2 channel currents and the increase of SK2 currents was inhibited by 5-HT4R.In condusion,HERV-W env could activate SK2 channels via decreased 5-HT4R,which might exhibit a novel mechanism for HERV-Wenv to influence neuronal activity in schizophrenia.

Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome

Background The 5-hydroxytryptamine7 receptor （5-HT7 receptor, 5-HTTR） plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome （IBS）. The aim of this study was to investigate the role of the 5-HT7 receptor in the pathogenesis of IBS. Methods A rat model of irritable bowel syndrome with diarrhea （IBS-D） was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation （IBS-C） was established by stomach irrigated with 0-4℃ cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT7 receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate （cAMP） in all the same tissues was measured by radioimmunity. Results The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon （P〈0.05）, as well as more than were found in the IBS-C group in jejunum and ileum （P〈0.05）. There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon （P〈0.05）. Real time-PCR results showed that the expression level of the 5-HT7 receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus （P〈0.05）. The expression level of 5-HT7 receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon （P〈0.05）. The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group （P〈0.01 and P〈0.05）. The cAMP accumulation in the tBS-C group was higher than that in the control group in the proximal and distal colon （m〈o.o5）. Conclusions The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT7 receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.

8-hydroxy-dipropylaminotetralin promotes neural plasticity in epileptic rats with depression

Rats with chronic pilocarpine-induced temporal lobe epilepsy complicated with depression were studied. Anti-5-bromodeoxyuridine immunofluorescence staining and Timms staining showed that neurogenesis within the hippocampal dentate gyrus and mossy fiber sprouting were increased in model rats. Neurogenesis within the hippocampal dentate gyrus was further enhanced, while mossy fiber sprouting was decreased in model rats administered carbamazepine alone or in combination with the 5-hydroxytryptamine 1A receptor agonist, 8-hydroxy-dipropylaminotetralin （0.1 and 1 mg/kg）. Among the groups, the effect was the most significant in rats receiving carbamazepine in conjunction with 1 mg/kg 8-hydroxy-dipropylaminotetralin. Thus, high dose 8-hydroxy-dipropylaminotetralin can improve neural plasticity in epileptic rats with depression.

Switching-on of serotonergic calcium signaling in activated hepatic stellate cells

AIM:To investigate serotonergic Ca 2+ signaling and the expression of 5-hydroxytryptamine(5-HT) receptors,as well as Ca 2+ transporting proteins,in hepatic stellate cells(HSCs) . METHODS:The intracellular Ca 2+ concentration([Ca 2+ ]i) of isolated rat HSCs was measured with a fluorescence microscopic imaging system.Quantitative PCR was per-formed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum(ER) proteins involved in Ca 2+ storage and release in cultured rat HSCs. RESULTS:Distinct from quiescent cells,activated HSCs exhibited[Ca 2+ ]i transients following treatment with 5-HT,which was abolished by U-73122,a phospholipase C inhibitor.Upregulation of 5-HT2A and 5-HT2B receptors,but not 5-HT3,was prominent during trans-differentiation of HSCs.Pretreatment with ritanserin,a 5-HT2 antagonist,inhibited[Ca 2+ ]i changes upon application of 5-HT.Expression of type 1 inositol-5'-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca 2+ storage and release in activated HSCs.Ca 2+ binding chaperone proteins of the ER,including calreticulin,calnexin and calsequestrin,were up-regulated following activation of HSCs. CONCLUSION:The appearance of 5-HT-induced[Ca 2+ ]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca 2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.

Neurotoxicity of prenatal alcohol exposure on medullary pre-B?tzinger complex neurons in neonatal rats

Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is unknown whether the 5-hydroxytryptamine 2A receptor（5-HT2AR） is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10%（v/v） throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2 AR protein and m RNA levels in the pre-B？tzinger complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduction was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10% alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These findings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2 AR protein and m RNA levels.

The antiemetic effects of magnetotherapy plus granisetron hydrochloride versus granisetron hydrochloride in patients with chemotherapy

Objective:The aim of this study was to observe and compare the antiemetic effectiveness and adverse events of magnetotherapy plus 5-hydroxytryptamine (5-HT3) receptor inhibitor granisetron hydrochloride vs granisetron hydrochloride alone in patients with chemotherapy.Methods:Sixty-four patients were randomized to receive either granisetron hydrochloride alone (control group:granisetron hydrochloride 3 mg intervenous infusion before chemotherapy, from the 1st day of chemotherapy course until the day after chemotherapy course completed) or magnetotherapy plus granisetron hydrochloride (treatment group:the same granisetron hydrochloride regimen plus rotatory magnetotherapy of 1 every day after chemotherapy for 5 begin with chemotherapy).Baseline characteristics were similar in both groups.The patients' emesia was evaluated according to WHO's criteria.The density of 5-HT3 was detected by enzyme-linked immunosorbent assay (ELISA).Results:In the treatment of acute vomiting, there was no significant difference between two groups (P>0.05), but in the treatment of tardive vomiting, the effectiveness in treatment group was better than that in control group (P<0.05).The density of 5-HT3 in treatment group and control group were (225.32±57.29) ng/mL vs (213.00 ±53.29) ng/mL before chemotherapy and (273.88 ±75.42) ng/mL vs (313.17±76.36) ng/mL after chemotherapy (P<0.01); the rate of adverse events was 36.36% and 48.39% respectively in treatment group and control group (P>0.05).Conclusion:Magnetotherapy plus granisetron hydrochloride provide better effectiveness than granisetron hydrochloride alone, and both therapies have synergistic effect.The adverse events didn't raised in treatment group.

Repeated generalized seizures shortly after single intramuscular dose is an additional reasonable cause to restrict the use of ondansetron: A case report

Background: Ondansetron, a 5-hydroxytryptamine (5-HT) receptor antagonist, is generally regarded as a safe and well tolerated antiemetic. Meanwhile, some reports mentioned that it is a probable cause of single generalized seizures after intravenous administration. Our report may be the first to indicate repeated generalized seizures after intramuscular therapeutic dose of ondansetron. Methods and Results: We report a 24-year-old female with nausea and vomiting related to gastritis that experienced repeated ondansetron-induced seizures shortly after a single intramuscular therapeutic dose. Two minutes after intramuscular injection of 4 mg ondansetron, our patient developed the first generalized seizure. Within the following two hours, seizures occurred two more times. In the emergency department, the patient developed a fourth, but weaker and shorter, generalized seizure. The patient was not hypoglycemic, but her blood hemoglobin and serum electrolytes were below normal. A few hours later, the patient was discharged. The dramatic onset of the seizures, as well as the complete recovery and absence of any neurological sequel in our patient, indicated that it was probably related to ondansetron. Conclusion: Patients should be informed about the potential side effects of ondansetron especially the life-threatening repeated generalized seizures, and clinicians should restrict its use to hospitalized patients.

Immunocytochemical localization of serotonin and its receptor on the rat hepatoma cell line

It has been found in recent years that neuropeptides and neurotransmitters do notexclusively occur in classical neuroendocrine cell tumors but also in many other tumortypes. Serotonin (5-hydroxytryptamine, 5-HT) has been detected in some cells of certain co-lon carcinomas. It has been proved that 5-HT stimulates cell proliferation of the