Hardcastle J, Hardcastle P T
Department of Biomedical Science, Sheffield University, UK.
J Pharm Pharmacol. 1995 Sep;47(9):744-9. doi: 10.1111/j.2042-7158.1995.tb06735.x.
The transintestinal potential difference (PD) across rat mid-small intestine and proximal colon was measured in-vivo. The 5-hydroxytryptamine (5-HT)-induced increase in PD, which reflects a stimulation of electrogenic C1 secretion, was mimicked by both 2-methyl-5-hydroxytryptamine (2-CH3-5-HT), an agonist at 5-HT3 receptors, and 5-methoxytryptamine (5-MT), an agonist that lacks affinity for 5-HT3 receptors. The 5-HT3 antagonist granisetron caused a marked inhibition of the response to 2-CH3-5-HT in both regions, but only produced a small inhibition of the small intestinal response to 5-HT, with a more pronounced effect in the colon. The failure of granisetron to produce a marked antagonism of the 5-HT-induced rise in the transintestinal PD, coupled with the ability of 5-MT to induce a secretory response, indicates that 5-HT3 receptors are not the only ones involved in the stimulation of C1 secretion. The 5-HT2 antagonist ketanserin failed to influence the response to 5-HT in either the small intestine or the colon, but it did inhibit the action of 5-MT, having a much greater effect in the small intestine. In the presence of granisetron however, ketanserin also inhibited the small intestinal response to 5-HT, having only a minimal effect in the colon. This suggests that 5-HT2 receptors can also play a role in the activation of C1 secretion. These observations suggest that both 5-HT2 and 5-HT3 receptors contribute to the stimulation of electrogenic C1 secretion by 5-HT, with 5-HT2 receptors playing a more prominent role in the small intestine and 5-HT3 receptors being more important in the colon.
在体内测量了大鼠中小肠和近端结肠的跨肠电位差（PD）。5-羟色胺（5-HT）诱导的PD增加反映了电中性氯离子分泌的刺激，5-HT3受体激动剂2-甲基-5-羟色胺（2-CH3-5-HT）和对5-HT3受体缺乏亲和力的激动剂5-甲氧基色胺（5-MT）均可模拟该增加。5-HT3拮抗剂格拉司琼在两个区域均显著抑制了对2-CH3-5-HT的反应，但仅对小肠对5-HT的反应产生轻微抑制，在结肠中的作用更明显。格拉司琼未能对5-HT诱导的跨肠PD升高产生明显拮抗作用，以及5-MT诱导分泌反应的能力，表明5-HT3受体不是刺激氯离子分泌的唯一受体。5-HT2拮抗剂酮色林未能影响小肠或结肠对5-HT的反应，但它确实抑制了5-MT的作用，在小肠中的作用更大。然而，在存在格拉司琼的情况下，酮色林也抑制了小肠对5-HT的反应，在结肠中的作用最小。这表明5-HT2受体也可在氯离子分泌激活中发挥作用。这些观察结果表明，5-HT2和5-HT3受体均有助于5-HT对电中性氯离子分泌的刺激，5-HT2受体在小肠中起更突出的作用，而5-HT3受体在结肠中更重要。
