5‐HT receptor subtypes involved in the stimulatory effect of 5‐HT on the peristaltic reflex in vitro

Abstract

Abstract The effect of serotonin (5‐HT) and of more selective 5‐HT agonists on the peristaltic reflex evoked in the isolated guinea‐pig ileum was investigated. Using the Trendelenburg technique, peristaltic contractions were elicited by increasing intraluminal pressure, and rhythmic contractions of the longitudinal and circular muscle were measured after serosal administration of the drugs. 5‐HT potently stimulated contractions of the longitudinal muscle. The effect of 5‐HT was partly antagonized by the 5‐HT 4 receptor antagonist SDZ 205–557. Of the potent 5‐HT 1A receptor agonists, 8‐OH‐DPAT, 5‐carboxamidotryptamine (5‐CT) and dipropyl‐5‐CT (DP‐5‐CT), only 5‐CT caused a substantial stimulation. Of the 5‐HT 1C ‐/5‐HT 2 receptor agonists DOI and 5‐methoxytryptamine (5‐MeOT), DOI was inactive, whereas 5‐MeOT potently stimulated contractions. 5‐HT 1D receptor agonists (5‐CT 1 sumatriptan) had a stimulatory effect. The effect of sumatriptan was antagonized by the 5‐HT 1D receptor antagonist metitepine but not by the 5‐HT 4 receptor antagonist SDZ 205–557. The 5‐HT 3 receptor agonist 2‐methyl‐5‐HT and the antagonists ICS 205–930 and granisetron did not influence the peristaltic reflex. 6‐OH‐indalpine, a 5‐HT 1P agonist, was inactive. This data suggest that 5‐HT stimulates the peristaltic reflex in the isolated guinea‐pig ileum by activation of 5‐HT 4 ‐ and 5‐HT 1D receptors; other 5‐HT receptor subtypes appear not to play a significant role in the modulation of this reflex.