5 ht4 (a)和5-HT4 (b)受体有几乎相同的药理学和都是表达人类心房和心室。
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巴赫T, Syversveen T, Kvingedal, Krobert KA, Brattelid T, Kaumann AJ,莱维FO
5 ht4 (a)和5-HT4 (b)受体有几乎相同的药理学和都是表达人类心房和心室。
Naunyn Schmiedebergs拱杂志。2001年2月,363 (2):146 - 60。
- PubMed ID
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11218067 (在PubMed]
- 文摘
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5 -羟色胺(5 -)增加人体心率和心房收缩力和加速心房放松通过5-HT4受体。此外,5 -可能arrhythmogenic和心房纤维性颤动。尚不清楚的剪接变体(s) 5-HT4受体表达和调节这些影响的5人的心里。先前的研究表明不同的药理性质5-HT4受体在人类心脏和鼠标丘神经元,可能是因为表达不同的剪接变体。因此我们克隆人类5-HT4 (b)受体和比较其药理特性与克隆人类5-HT4 (a)受体和寻找相应的mRNA在人体组织。两个人类5-HT4受体的主要结构拼接变体是相同的除了发散28和29个氨基酸的c端尾5-HT4 (a)和5-HT4 (b)受体,分别。逆转录-聚合酶链反应(rt - pcr)分析表明,变异都是coexpressed各组织,包括心脏心房和心室。额外的乐队提出的存在两个以上的人类5-HT4受体拼接变体。稳定与克隆受体表达在HEK293细胞或瞬变COS-7表达细胞,[3 h] GR 113808始终显示略高亲和力h5-HT4 (b)比h5-HT4 (a)受体(pKd 0.1高-0.2日志单位)。受体激动剂的竞争,部分受体激动剂和拮抗剂[3 h] GR113808绑定显示这两个受体之间没有显著差异。 For 5-HT4 receptor agonists and antagonists, their potencies in stimulating or inhibiting, respectively, 5-HT-stimulated adenylyl cyclase activity correlated well with their binding affinities. Tropisetron and SB207710 showed partial agonist activity at high receptor expression levels for both isoforms. Cisapride and renzapride were both partial agonists at moderate receptor levels and full agonists at high receptor levels. Cisapride was more potent than renzapride while the converse was the case in human atrium, for which cisapride had lower affinity and agonist potency than at the recombinant receptors. The binding affinities and agonist potencies of ligands for both 5-HT4(a) and 5-HT4(b) receptors correlated with the corresponding affinities and potencies in human atrium. The agonist potency of SB207710 was around 10 times lower than its binding and blocking affinity for both splice variants, suggesting that activation of adenylyl cyclase and blockade of 5-HT responses are mediated through different conformational states. The similar pharmacological properties of the two human 5-HT4 receptor splice variants together with their expression in human atrium would be consistent with mediation of the cardiostimulant effects of 5-HT through both variants. However, the effects of cisapride appear either mediated through non-a and non-b splice variants of the 5-HT4 receptor or 5-HT4(a) and 5-HT4(b) receptor expression in human atrial cells alters somewhat their pharmacological profile through still unknown mechanisms.