Investigation into the 5-hydroxytryptophan-evoked luminal 5-hydroxytryptamine release from the guinea pig colon.
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 microM) concentration-dependently caused an increase of the luminal outflow of 5-HT. Either tetrodotoxin (0.3 microM) or atropine (0.2 microM) did not affect the 5-HTP-evoked increase in luminal 5-HT outflow, while the L-type calcium channel blocker, nicardipine (1 microM) or diltiazem (1 microM) reduced the 5-HTP-evoked 5-HT outflow by 47% and 61%, respectively. SB203186 (1 microM), a 5-HT4-receptor antagonist, enhanced the 5-HTP-evoked 5-HT outflow, while ramosetron (1 microM), a 5-HT3-receptor antagonist reduced the stimulating effect of 5-HTP by 66%. Ketanserin (0.1 microM), 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.
Kojima
S
S
Department of Pharmacology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan. s-kojima@dokkyomed.ac.jp
Ikeda
M
M
Kamikawa
Y
Y
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D000818:Animals; D003106:Colon / Q000378:metabolism*; D004759:Enterochromaffin Cells / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006916:5-Hydroxytryptophan