Investigation Into the 5-Hydroxytryptophan-Evoked Luminal 5-Hydroxytryptamine Release From the Guinea Pig Colon

Abstract

The effect of an endogenous 5−hydroxytryptamine(5−HT)precursor, 5−hydroxytryptophan(5−HTP), on the luminal outflow of 5−HT was examined using the luminally perfused isolated colon of the guinea pig, a model that would facilitate the pharmacological analysis of luminal 5−HT release from enterochromaffin cells(EC cells).5−HTP(1−10μM)concentration−dependently caused an increase of the luminal outflow of 5−HT.Either tetrodotoxin(0.3μM)or atropine(0.2μM)did not affect the 5−HTP−evoked increase in luminal 5−HT outflow, while the L−type calcium channel blocker, nicardipine(1μM)or diltiazem(1μM)reduced the 5−HTP−evoked 5−HT outflow by 47% and 61%, respectively.SB203186(1μM), a 5−HT₄−receptor antagonist, enhanced the 5−HTP−evoked 5−HT outflow, while ramosetron(1μM), a 5−HT₃−receptor antagonist reduced the stimulating effect of 5−HTP by 66%.Ketanserin(0.1μM), a 5−HT_2A−receptor antagonist did not modify the stimulatory effect of 5−HTP.It is concluded that in the guinea pig colon, 5−HTP facilitates the luminal 5−HT release from EC cells, with no involvement of neuronal mechanisms and a non−neuronal cholinergic system.Furthermore, non−neuronal 5−HT₃ and 5−HT₄ receptors appear to contribute to the regulation of the luminal 5−HT release evoked by 5−HTP.This new bioassay of the guinea pig colon allows the pharmacological characterization of uncomplicated luminal 5−HT release from EC cells.