Shu-ichi Kojima1,*, Masashi Ikeda2 and Yuichiro
Kamikawa1
1Departmentﾊof Pharmacology, 2Laboratory of Medical
Science, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan
*Corresponding author.ﾊﾊFAX:+81-282-86-2915
E-mail: s-kojima@dokkyomed.ac.jp
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ﾊmM)
concentration-dependently caused an increase of the luminal outflow of 5-HT.
Either tetrodotoxin (0.3ﾊmM) or atropine (0.2ﾊmM)
did not affect the 5-HTP-evoked increase in luminal 5-HT outflow, while
the L-type calcium channel blocker, nicardipine (1ﾊmM)
or diltiazem (1ﾊmM) reduced the 5-HTP-evoked
5-HT outflow by 47% and 61%, respectively. SB203186 (1ﾊmM),
a 5-HT4-receptor antagonist, enhanced the 5-HTP-evoked 5-HT outflow,
while ramosetron (1ﾊmM), a 5-HT3-receptor
antagonist reduced the stimulating effect of 5-HTP by 66%. Ketanserin (0.1ﾊ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
Copyrightｩ The Japanese Pharmacological Society 2000
[Back to TOC]