对豚鼠回肠中介导收缩和诱发[3H] - 乙酰胆碱释放的5 - HT3受体的研究。
An examination of the 5-HT3 receptor mediating contraction and evoked [3H]-acetylcholine release in the guinea-pig ileum.
作者信息
Fox A, Morton I K
机构信息
Division of Biomedical Sciences, King's College London.
出版信息
Br J Pharmacol. 1990 Nov;101(3):553-8. doi: 10.1111/j.1476-5381.1990.tb14119.x.
Abstract
- The relative contributions of two classes of 5-hydroxytryptamine (5-HT) receptor (5-HT2 and 5-HT3) to the contractile action of 5-HT, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) were studied in the guinea-pig ileum longitudinal muscle-myenteric plexus strip (LMMP) preparation. Contractility studies were combined with an analysis of the effects of the three agonists on [3H]-acetylcholine ([3H]-ACh) release from preparations preincubated with [3H]-choline. 2. In contracting the LMMP, 5-HT was approximately one order of magnitude more active than 2-methyl-5-HT and alpha-methyl-5-HT, with relative activities for 5-HT: 2-methyl-5-HT: alpha-methyl-5-HT of 1.00: 0.13: 0.10. 3. Ketanserin (1 microM) was without effect on the concentration-response curves for concentration to 5-HT. 2-methyl-5-HT or alpha-methyl-5-HT, whilst ondansetron (GR38032F: 1 microM) produced a parallel rightward displacement of the upper part of the concentration-response curves to 5-HT and alpha-methyl-5-HT and of the entire curve to 2-methyl-5-HT. 4. In increasing the spontaneous release of [3H]-ACh from the LMMP, 5-HT was again approximately one order of magnitude more active than 2-methyl-5-HT and alpha-methyl-5-HT with relative activities for 5-HT: 2-methyl-5-HT: alpha-methyl-5-HT of 1.00: 0.19: 0.11. 5. Ondansetron (1 microM) greatly attenuated the increase in spontaneous [3H]-ACh release evoked by all three agonists. pKB estimates of 7.62 + 0.12 and 7.64 + 0.09 were obtained for ondansetron antagonism of 5-HT and 2-methyl-5-HT-evoked increases respectively. 6. These data suggest that the contractile action of 5-HT, 2-methyl-5-HT and a-methyl-5-HT in the guinea-pig ileum can, under these conditions, be accounted for largely in terms of 5-HT3 receptor activation. Estimates for pKB obtained with ondansetron are in accordance with those previously obtained from contractility studies in this preparation and these findings are discussed in terms of the postulated existence of subtypes of 5-HT3 receptors.
摘要
在豚鼠回肠纵肌-肠肌丛条（LMMP）标本中，研究了两类5-羟色胺（5-HT）受体（5-HT2和5-HT3）对5-HT、2-甲基-5-羟色胺（2-甲基-5-HT）和α-甲基-5-羟色胺（α-甲基-5-HT）收缩作用的相对贡献。收缩性研究与分析这三种激动剂对用[3H]-胆碱预孵育的标本中[3H]-乙酰胆碱（[3H]-ACh）释放的影响相结合。
在使LMMP收缩方面，5-HT的活性比2-甲基-5-HT和α-甲基-5-HT大约高一个数量级，5-HT:2-甲基-5-HT:α-甲基-5-HT的相对活性为1.00:0.13:0.10。
酮色林（1微摩尔）对5-HT、2-甲基-5-HT或α-甲基-5-HT的浓度-反应曲线无影响，而昂丹司琼（GR38032F：1微摩尔）使5-HT和α-甲基-5-HT浓度-反应曲线上部以及2-甲基-5-HT的整个曲线平行右移。
在增加LMMP中[3H]-ACh的自发释放方面，5-HT的活性再次比2-甲基-5-HT和α-甲基-5-HT大约高一个数量级，5-HT:2-甲基-5-HT:α-甲基-5-HT的相对活性为1.00:0.19:0.11。
昂丹司琼（1微摩尔）极大地减弱了所有三种激动剂引起的[3H]-ACh自发释放的增加。分别获得昂丹司琼拮抗5-HT和2-甲基-5-HT引起的增加的pKB估计值为7.62±0.12和7.64±0.09。
这些数据表明，在这些条件下，5-HT、2-甲基-5-HT和α-甲基-5-HT在豚鼠回肠中的收缩作用在很大程度上可归因于5-HT3受体的激活。用昂丹司琼获得的pKB估计值与先前在该标本中进行的收缩性研究中获得的值一致，并且根据5-HT3受体亚型的假定存在对这些发现进行了讨论。
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