5-HT receptor subtypes involved in luminal serotonin-induced secretion in rat intestine in vivo

The purpose of this study was to compare the 5-hydroxytryptamine (5-HT) receptor subtypes involved in secretion of water and electrolytes (sodium, potassium, and chloride) induced by luminally administered serotonin in rat jejunum and ileum in vivo. Ketanserin partially inhibited and ICS 205-930 totally inhibited serotonin-evoked secretion. Ketanserin induced mild basal secretion while ICS 205-930 alone reduced basal absorption. There were no differences in the effects of ketanserin or ICS 205-930 on serotonin-induced secretion by rat jejunum versus ileum. Neither N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide nor methysergide altered the secretory effect of serotonin in rat ileum. The substituted benzamides, cisapride, and BRL 24924, and the 5-HT4 agonist, 5-methoxytryptamide, induced water and electrolyte secretion. While BRL 24924 did not alter the subsequent serotonin-induced secretory fluxes, cisapride slightly inhibited the induced secretion. These results suggest that (1) in both segments of the intestine, 5-HT2, 5-HT3, and/or 5-HT4 receptor subtypes are involved in the regulation of intestinal transport of water and electrolytes under basal conditions; (2) serotonin-induced water and electrolyte secretion is mediated by pathways involving 5-HT2, 5-HT3, and 5-HT4 receptor subtypes in both rat jejunum and ileum; (3) 5-HT1 receptors do not seem to be involved in the mediation of intestinal water and electrolyte transport; (4) these effects are similar to those described for systemically administered 5-HT.