对源自豚鼠组织的三种离体标本中5-羟色胺3受体的药理学特性进行研究。
The pharmacological characterization of 5-HT3 receptors in three isolated preparations derived from guinea-pig tissues.
作者信息
Butler A, Elswood C J, Burridge J, Ireland S J, Bunce K T, Kilpatrick G J, Tyers M B
机构信息
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Hertfordshire.
出版信息
Br J Pharmacol. 1990 Nov;101(3):591-8. doi: 10.1111/j.1476-5381.1990.tb14126.x.
Abstract
- The pharmacological characterization of the 5-HT3 receptors in guinea-pig isolated tissues is described. The tissues used were ileum (longitudinal muscle-myenteric plexus), colon and vagus nerve. The guinea-pig isolated colon is a novel preparation. 2. In the guinea-pig isolated ileum, 5-hydroxytryptamine (5-HT, 1 x 10(-8)-3 x 10(-5) M) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (3 x 10(-7)-1 x 10(-4) M) caused concentration-related contractions. The 5-HT concentration-response curve was biphasic whilst the 2-methyl-5-HT curve was monophasic. The EC50 value for the low potency portion of the 5-HT curve was 4.1 x 10(-6) M. The EC50 for 2-methyl-5-HT was 1.23 x 10(-5) M. Selective 5-HT3 receptor antagonists caused rightward shifts of the 2-methyl-5-HT curve and the lower potency portion of the 5-HT curve. Neither ketanserin (1 x 10(-6) M) nor methysergide (1 x 10(-5) M) antagonized the responses to 5-HT or 2-methyl-5-HT. 3. In the guinea-pig isolated colon, 5-HT (3 x 10(-7)-3 x 10(-5) M; EC50 2.4 x 10(-6) M) caused contractions which were mimicked by 2-methyl-5-HT (1 x 10(-6)-1 x 10(-4) M; EC50 7.2 x 10(-6) M). Selective 5-HT3 receptor antagonists caused rightward displacements of the 5-HT concentration-response curves. Neither ketanserin (1 x 10-6 M) nor methysergide (1 x 10- 5M) had any effect on responses to 5-HT or 2-methyl- 5-HT. 4. In the guinea-pig isolated vagus nerve, 5-HT (1 x 10-6-3 x 1O-4M) and 2-methyl-5-HT (1 x i0-S- 1 X 10-3m; EC50 7.6 x 10- M) caused depolarizations; at higher concentrations there were afterhyperpolarizations. The maximum response to 2-methyl-5-HT was less than half that to 5-HT. Selective 5-HT3 receptor antagonists caused rightward displacements of the 5-HT concentration-response curves. Antagonists at other 5-HT receptors (ketanserin, 1 x 10- M and methysergide, 1 x 10-6 M) had no effect. 5. The estimated affinity values of 5-HT3 receptor antagonists correlated well between the three models. Phenylbiguanide was inactive as an agonist or antagonist (up to 1 x 1O-4M) in each preparation. 6. Comparisons with antagonist affinity values obtained in the rat isolated vagus nerve revealed marked differences. Antagonists were generally more potent on the rat isolated vagus nerve, although the differences varied considerably between antagonists. 7. The results are discussed in terms of species-related receptor differences.
摘要
- 本文描述了豚鼠离体组织中5-羟色胺3（5-HT3）受体的药理学特征。所用组织为回肠（纵行肌-肠肌丛）、结肠和迷走神经。豚鼠离体结肠是一种新的制备物。2. 在豚鼠离体回肠中，5-羟色胺（5-HT，1×10⁻⁸ - 3×10⁻⁵ M）和选择性5-HT3受体激动剂2-甲基-5-HT（3×10⁻⁷ - 1×10⁻⁴ M）引起浓度依赖性收缩。5-HT浓度-反应曲线呈双相性，而2-甲基-5-HT曲线呈单相性。5-HT曲线低效能部分的半数有效浓度（EC50）值为4.1×10⁻⁶ M。2-甲基-5-HT的EC50为1.23×10⁻⁵ M。选择性5-HT3受体拮抗剂使2-甲基-5-HT曲线以及5-HT曲线的低效能部分向右移位。酮色林（1×10⁻⁶ M）和麦角新碱（1×10⁻⁵ M）均未拮抗对5-HT或2-甲基-5-HT的反应。3. 在豚鼠离体结肠中，5-HT（3×10⁻⁷ - 3×10⁻⁵ M；EC50 2.4×10⁻⁶ M）引起收缩，2-甲基-5-HT（1×10⁻⁶ - 1×10⁻⁴ M；EC50 7.2×10⁻⁶ M）可模拟该收缩。选择性5-HT3受体拮抗剂使5-HT浓度-反应曲线向右移位。酮色林（1×10⁻⁶ M）和麦角新碱（1×10⁻⁵ M）对5-HT或2-甲基-5-HT的反应均无影响。4. 在豚鼠离体迷走神经中，5-HT（1×10⁻⁶ - 3×10⁻⁴ M）和2-甲基-5-HT（1×10⁻⁵ - 1×10⁻³ M；EC50 7.6×10⁻⁵ M）引起去极化；在较高浓度时出现超极化后电位。对2-甲基-5-HT的最大反应小于对5-HT最大反应的一半。选择性5-HT3受体拮抗剂使5-HT浓度-反应曲线向右移位。其他5-HT受体拮抗剂（酮色林，1×10⁻⁶ M和麦角新碱，1×10⁻⁶ M）无作用。5. 在三种模型中，5-HT3受体拮抗剂的估计亲和力值相关性良好。苯乙双胍在每种制剂中作为激动剂或拮抗剂均无活性（浓度高达1×10⁻⁴ M）。6. 与在大鼠离体迷走神经中获得的拮抗剂亲和力值比较显示出显著差异。拮抗剂在大鼠离体迷走神经上通常更有效，尽管不同拮抗剂之间差异很大。7. 根据物种相关的受体差异对结果进行了讨论。
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