Jpn. J. Pharmacol. 84 (2), 174-178 (2000)

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

Shu-ichi Kojima1,*, Masashi Ikeda2 and Yuichiro Kamikawa1

1Department╩of Pharmacology, 2Laboratory of Medical Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan
*Corresponding author.╩╩FAX:+81-282-86-2915

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 (1-10╩mM) concentration-dependently caused an increase of the luminal outflow of 5-HT. Either tetrodotoxin (0.3╩mM) or atropine (0.2╩mM) did not affect the 5-HTP-evoked increase in luminal 5-HT outflow, while the L-type calcium channel blocker, nicardipine (1╩mM) or diltiazem (1╩mM) reduced the 5-HTP-evoked 5-HT outflow by 47% and 61%, respectively. SB203186 (1╩mM), a 5-HT4-receptor antagonist, enhanced the 5-HTP-evoked 5-HT outflow, while ramosetron (1╩mM), a 5-HT3-receptor antagonist reduced the stimulating effect of 5-HTP by 66%. Ketanserin (0.1╩mM), a 5-HT2A-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.

Keywords: 5-Hydroxytryptamine (serotonin), Colon, Enterochromaffin cell, 5-Hydroxytryptophan

Copyrightę The Japanese Pharmacological Society 2000

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