Pathways of serotonin-induced electrolyte transport in rat distal colon.

Abstract

Serotinin-stimulated electrolyte transport was examined in flat-sheet preparations of rat left colon with the Ussing chamber-voltage clamp technique. Transport was studied in tissues stripped of muscularis propria and in nonstripped tissue. In nonstripped colon, the action of serotonin (5-hydroxytrytamine [5-HT]) on short-circuit current was inhibited by a factor of 60% by tetrodotoxin (P less than 0.05; t test) and was also inhibited by the 5HT2 antagonist ketanserin (p less than 0.05 vs serotonin; t test) and the 5-HT3 antagonist ICS 205-930 (p less than 0.05 vs serotonin, t test). These compounds produced corresponding inhibition of serotonin-induced sodium and chloride flux in this preparation. The tetrodotoxin-sensitive component was not inhibited by atropine, hexamethonium, phentolamine, or propranolol. Histologic analysis of the stripped preparation showed that it consisted of mucosa and musclaris mucosa only. In this stripped preparation, serotonin-induced change in short-circuit current was tetrodotoxin insensitive and inhibited by ketanserin (p less than 0.05 vs serotonin, t test) but not by ICS 205-930. Serotonin-induced sodium and chloride flux was inhibited by ketanserin in the presence of tetrodotoxin in this preparation. These results suggest that serotonin-induced electrolyte transport in rat distal colon is mediated by nonneural 5HT2 receptors in the mucosa or muscularis mucosa and by 5-HT3 receptors located on enteric nonadrenergic, noncholinergic nerves.