Sevcík J, Ruzicka V, Slánsky J, Masek K
Institute of Pharmacology, Academy of Sciences of the Czech Republic, Prague.
Methods Find Exp Clin Pharmacol. 1996 Sep;18(7):421-30.
Concentration-dependent 5-hydroxytryptamine (5-HT) relaxations of guinea pig proximal colon were evoked in the presence of atropine (0.2 microM). 5-HT effect was neuronally mediated since it was blocked by tetrodotoxin (TTX) (0.5 microM). The type of 5-HT receptor mediating the relaxations was investigated using both 5-HT agonists and antagonists. Selective 5-HT3 antagonists tropisetron (10, 50, 500 nM) and ondansetron (1 microM) shifted the concentration-response curves for 5-HT to the right. Another 5-HT3 antagonist MDL 72222 (0.5 microM), 5-HT1/5-HT2 antagonists methiothepin (0.1 microM) and metergoline (0.1 microM), 5-HT(1A,B) antagonist propranolol (l microM) and 5-HT1B antagonist isamoltane (10 nM) were ineffective. Specific agonist of 5-HT3 receptors 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and agonist of 5-HT1 receptors 5-carboxamidotryptamine (5-CT) also relaxed the preparation, although the relaxation was not 5-HT relaxation. Neither was it neurogenic because it persisted in the presence of TTX (0.5 microM). The concentration-response curve for 2-methyl-5-HT was not affected by ondansetron (1 microM) or tropisetron (0.5 microM), but it was shifted to the right in the presence of 5-HT1/5-HT2 receptor antagonists methiothepin (0.1 microM) and metergoline (0.1 microM) and in the presence of 5-HT(1Da)/5-HT2A receptor antagonist ketanserin (1 microM). Methiothepin (0.1 microM) also inhibited the relaxations evoked in the presence of 5-CT. Specific agonist of 5-HT4 receptors 5-methoxytryptamine did not exert any effect on the preparation. It is suggested that there are two different mechanisms of relaxation in the guinea pig proximal colon. One is neurogenic and involves the activation of 5-HT3 receptors located on inhibitory neurons to the muscle; the other is myogenic and might be mediated via yet unclassified 5-HT receptors located on the muscle.
在存在阿托品（0.2微摩尔）的情况下，豚鼠近端结肠出现了浓度依赖性的5-羟色胺（5-HT）舒张反应。5-HT的作用是由神经介导的，因为它被河豚毒素（TTX）（0.5微摩尔）阻断。使用5-HT激动剂和拮抗剂研究了介导舒张反应的5-HT受体类型。选择性5-HT3拮抗剂托烷司琼（10、50、500纳摩尔）和昂丹司琼（1微摩尔）使5-HT的浓度-反应曲线右移。另一种5-HT3拮抗剂MDL 72222（0.5微摩尔）、5-HT1/5-HT2拮抗剂甲硫噻嗪（0.1微摩尔）和麦角新碱（0.1微摩尔）、5-HT(1A,B)拮抗剂普萘洛尔（1微摩尔）和5-HT1B拮抗剂异莫他烷（10纳摩尔）无效。5-HT3受体特异性激动剂2-甲基-5-羟色胺（2-甲基-5-HT）和5-HT1受体激动剂5-羧酰胺色胺（5-CT）也使标本舒张，尽管这种舒张不是5-HT介导的舒张。它也不是神经源性的，因为在存在TTX（0.5微摩尔）时它仍然存在。2-甲基-5-HT的浓度-反应曲线不受昂丹司琼（1微摩尔）或托烷司琼（0.5微摩尔）的影响，但在存在5-HT1/5-HT2受体拮抗剂甲硫噻嗪（0.1微摩尔）和麦角新碱（0.1微摩尔）以及存在5-HT(1Da)/5-HT2A受体拮抗剂酮色林（1微摩尔）时右移。甲硫噻嗪（0.1微摩尔）也抑制了在存在5-CT时诱发的舒张反应。5-HT4受体特异性激动剂5-甲氧基色胺对标本没有任何作用。提示豚鼠近端结肠存在两种不同的舒张机制。一种是神经源性的，涉及激活位于对肌肉的抑制性神经元上的5-HT3受体；另一种是肌源性的，可能是通过位于肌肉上尚未分类的5-HT受体介导的。
