Budhoo M R, Harris R P, Kellum J M
Department of Surgery, Medical College of Virginia, Richmond 23298, USA.
Eur J Pharmacol. 1996 Mar 7;298(2):137-44. doi: 10.1016/0014-2999(95)00752-0.
In the rat distal colon, 5-hydroxytryptamine (5-HT)-induced Cl- secretion is seen as a rise in short circuit current (Isc). We investigated the 5-HT receptor mediating 5-HT-induced Cl- secretion in the rat distal colon. Rat distal colon was prepared either by stripping away the muscularis propria with the neural ganglia, or by leaving it intact. The tissue was mounted in Ussing chambers and short circuited. 5-HT receptor agonist-induced changes (delta) in Isc were recorded in the presence and absence of 5-HT receptor antagonists. In stripped preparations, the rank order of potency of agonists was: 5-HT > 5-methoxytryptamine > alpha-methyl-5-HT >> 2-methyl-5-HT. 5-HT and 5-methoxytryptamine-induced changes in Isc were antagonized by > or = 0.3 microM tropisetron with pA2 values 6.5 and 6.4, respectively. The 5-HT4 antagonist, SC 53606, antagonized the 5-HT-induced response with a pA2 of 7.2. 5-HT1-like (methysergide), 5-HT1P (N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide (5-HTP-DP)), 5-HT2A (ketanserin) and 5-HT3 (ondansetron) receptor antagonists had no significant effect on the 5-HT response in stripped tissue. 3 microM forskolin, or 10 microM 3-isobutyl-1-methyl-xanthine (IBMX), decreased the EC50 and increased the maximum 5-HT response. The 2-methyl-5-HT and 5-HT-induced delta Isc in the unstripped colon preparation were antagonized by the 5-HT3 antagonist, ondansetron (0.3 nM), and 2-methyl-5-HT activity was abolished by pretreatment with tetrodotoxin. In conclusion, 5-HT-induced delta Isc is neurally mediated via a 5-HT3 receptor, and non-neurally mediated via a 5-HT4 receptor in the rat distal colon.
在大鼠远端结肠中，5-羟色胺（5-HT）诱导的氯离子分泌表现为短路电流（Isc）升高。我们研究了介导大鼠远端结肠中5-HT诱导的氯离子分泌的5-HT受体。大鼠远端结肠的制备方法有两种：一种是剥离带有神经节的固有肌层，另一种是保持其完整。将组织安装在尤斯灌流小室中并进行短路处理。在存在和不存在5-HT受体拮抗剂的情况下，记录5-HT受体激动剂诱导的Isc变化（δ）。在剥离的标本中，激动剂的效价顺序为：5-HT＞5-甲氧基色胺＞α-甲基-5-HT＞＞2-甲基-5-HT。5-HT和5-甲氧基色胺诱导的Isc变化分别被≥0.3μM的托烷司琼拮抗，其pA2值分别为6.5和6.4。5-HT4拮抗剂SC 53606以7.2的pA2拮抗5-HT诱导的反应。5-HT1样（麦角新碱）、5-HT1P（N-乙酰-5-羟色氨酰5-羟色氨酸酰胺（5-HTP-DP））、5-HT2A（酮色林）和5-HT3（昂丹司琼）受体拮抗剂对剥离组织中的5-HT反应无显著影响。3μM的福斯高林或10μM的3-异丁基-1-甲基黄嘌呤（IBMX）降低了5-HT的半数有效浓度（EC50）并增加了最大反应。在未剥离的结肠标本中，2-甲基-5-HT和5-HT诱导的δIsc被5-HT3拮抗剂昂丹司琼（0.3 nM）拮抗，并且用河豚毒素预处理可消除2-甲基-5-HT的活性。总之，在大鼠远端结肠中，5-HT诱导的δIsc通过5-HT3受体由神经介导，通过5-HT4受体由非神经介导。
