A 5-HT2 receptor mediates serotonin-induced electrolyte transport in rat left colon.

Serotonin (5-hydroxytryptamine, 5-HT) is a potent mediator of diarrhea in the carcinoid syndrome. However, the mechanisms of serotonin-induced intestinal secretion remain unclear. The purpose of this study was to determine whether 5-HT stimulates electrolyte transport by a direct action at a mucosal receptor. Serotonin-stimulated electrolyte transport was studied in flat sheet preparations of rat left colon using flux chambers. 5-HT stimulated a concentration-dependent rise in short-circuit current in sheets stripped of muscularis propria. The half-maximal concentration required to produce this effect was 50 microM. The preferential 5-HT2 antagonist ketanserin produced a rightward shift of the serotonin concentration-response curve with a pA2 value of 7.7. Serotonin stimulated electrolyte transport by inhibiting mucosa to serosa movement of both sodium and chloride. The 5-HT1 antagonist N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide and the 5-HT3 antagonist 3-tropanyl-indole-3-carboxylate methiodide had no effect on these actions of serotonin on electrolyte transport. In contrast, ketanserin inhibited the actions of serotonin on both sodium and chloride movement and inhibited the rise in short-circuit current induced by 100 microM 5-HT. This study demonstrates that a 5-HT2 receptor located in the vicinity of the mucosa is involved in the regulation of serotonin-stimulated intestinal electrolyte transport.