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1.
Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs 总被引:1,自引:0,他引:1
Hiroki Morita Erito Mochiki Nobuyuki Takahashi Kiyoshi Kawamura Akira Watanabe Toshinaga Sutou Atsushi Ogawa Mitsuhiro Yanai Kyoichi Ogata Takaaki Fujii Tetsuro Ohno Souichi Tsutsumi Takayuki Asao Hiroyuki Kuwano 《World journal of gastroenterology : WJG》2013,19(39):6604-6612
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. 相似文献
2.
肿瘤坏死因子-α增强肾小球前小动脉平滑肌细胞内I型三磷酸肌醇受体的表达 总被引:7,自引:0,他引:7
目的 探讨肿瘤坏死因子-α(TNF-α)对肾小球前小动脉平滑肌细胞(RASMC)I型三磷酸肌醇(IP3)受体蛋白表达的影响。方法 通过对RASMC的分离、培养和鉴定,应用蛋白和核酸杂交技术分别检测TNF-α作用后RASMC中I型IP3受体蛋白和I型IP3受体mRAN的表达情况,同时测定I型IP3受体mRNA的半衰期。结果 TNF-α能增强RASMC内I型IP3受体蛋白的表达,且两者呈剂量依赖关系;TNF-α能促进I型IP3受体mRNA的表达,同时使受体蛋白合成增加;而TNF-α对I型IP3受体mRNA的影响不是抑制mRNA的降解,而是使其表达增加。结论 TNF-α可能作用于I型IP3受体mRNA的基因启动子,使其合成增加,由此导致I型IP3受体蛋白表达增加,诱导RASMC内储备的Ca^2 释放至细胞浆,引起肾小球前小动脉平滑肌细胞收缩,使肾血流量减少,肾小球滤过率下降,从而导致肾功能异常。 相似文献
3.
Effects of a serotonin 5-HT(4) receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans 总被引:9,自引:0,他引:9
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Bharucha AE Camilleri M Haydock S Ferber I Burton D Cooper S Tompson D Fitzpatrick K Higgins R Zinsmeister AR 《Gut》2000,47(5):667-674
BACKGROUND: Serotonin 5-HT(4) receptors are located on enteric cholinergic neurones and may regulate peristalsis. 5-HT(4) receptors on primary afferent neurones have been postulated to modulate visceral sensation. While 5-HT(4) agonists are used as prokinetic agents, the physiological role of 5-HT(4) receptors in the human gut is unknown. AIMS: Our aim was to characterise the role of 5-HT(4) receptors in regulating gastrointestinal motor and sensory function in healthy subjects under baseline and stimulated conditions with a 5-HT(4) receptor antagonist. METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects. In part B, 52 healthy subjects received placebo, or 0.05, 0.5, or 5 mg of SB-207266 for 10-12 days; gastric, small bowel, and colonic transit were measured by scintigraphy on days 7-9, and fasting and postprandial colonic motor function, compliance, and sensation during distensions were assessed on day 12. RESULTS: Part A: 0.5, 5, and 20 mg doses of SB-207266 had significant and quantitatively similar effects, antagonising the cisapride mediated increase in plasma aldosterone and acceleration of orocaecal transit. Part B: SB-207266 tended to delay colonic transit (geometric centre of isotope at 24 (p=0.06) and 48 hours (p=0.08)), but did not have dose related effects on transit, fasting or postprandial colonic motor activity, compliance, or sensation. CONCLUSION: 5-HT(4) receptors are involved in the regulation of cisapride stimulated orocaecal transit; SB 207266 tends to modulate colonic transit but not sensory functions or compliance in healthy human subjects. 相似文献
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目的 研究心脏瓣膜病心房颤动(房颤)患者左心房肌超极化激活环化核苷酸门控通道(HCN)各亚型及其调节受体5-羟色胺4受体(5-HT4-R)基因表达及蛋白表达.方法 86例心脏瓣膜置换术后患者,窦性心律38例,房颤48例,术中取左心耳组织,用实时定量聚合酶链反应( PCR)和蛋白免疫印记法( western blot)的方法测定HCN通道各亚型及5-HT4-R基因表达和蛋白表达.结果 同窦性心律组相比,房颤组患者心房肌HCN2、HCN4的mRNA表达及蛋白表达水平上调,5-HT4-R mRNA表达及蛋白表达水平下调,HCN1的mRNA表达及蛋白表达在房颤组患者中亦有增高,但差异无统计学意义.HCN2的mRNA表达及蛋白表达与左心房内径呈正相关.5-HT4-R mRNA表达水平下调与左心房内径呈负相关.结论 左心房肌HCN2、HCN4的mRNA表达及蛋白表达上调及5-HT4-RmRNA表达及蛋白表达水平下调可能是瓣膜病房颤患者左心房肌电重构的分子基础之一. 相似文献
5.
目的 检测不同鼠龄SD大鼠肠道推进率、肠道黏膜嗜铬细胞数量和肠肌间神经丛5-羟色胺受体3(5-HT3R)的表达,探讨生理性衰老过程中肠道运动功能变化的规律及其机制. 方法 80只健康SD大鼠分为3月龄、9月龄、18月龄、24月龄及30月龄5组,每组各16只.以印度墨汁为标记物,检测大鼠的肠道推进率;采用免疫组化链霉亲和素-生物素-过氧化物酶复合物(SABC)法染色,检测大鼠空肠、回肠和结肠黏膜及黏膜下嗜铬细胞的数量以及肠肌间神经丛5-HT3R的表达.结果肠道推进率30月龄组大鼠为(52.1±9.8)%,明显低于3月龄组(67.2±13.5)%(t=7.013,P=0.001);30月龄组大鼠空肠、回肠及结肠黏膜和黏膜下嗜铬细胞数量分别为(11.1±3.0)个、(10.6±1.9)个和(10.2±4.3)个,较3月龄组(22.9±6.2)个、(25.8±7.1)个和(23.0±5.7)个减少(t=3.640,t=3.384,t=4.154,均为P<0.01);大鼠空肠和结肠的5-HT3R表达30月龄组分别为4.8±1.4和9.3±4.2,较9月龄组的8.9±1.5和14.5±5.3减少(t=3.464,t=3.003,均为P<0.01),回肠5-HT3R 30月龄组和3月龄组分别为5.0±1.3和9.0±1.7(t=4.549,P<0.001). 结论 老年大鼠肠道推进率、肠道嗜铬细胞数量及肠肌间神经丛5-HT3R表达均显著降低,并随年龄增长而逐渐明显;老年大鼠肠道运动功能的明显下降与肠嗜铬细胞数量以及肌间神经丛5-HT3R的表达显著降低有一定的相关性. 相似文献