Mayumi Yamano, Hiroyuki Ito and Keiji Miyata
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi
Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305, Japan
Abstract: We investigated the mechanism of 5-hydroxytryptamine
(5-HT)-induced contraction in the longitudinal muscle of isolated distal
ileum from ferrets, piglets and rats. 5-HT and 5-methoxytryptamine concentration-dependently
contracted the ileum of ferrets, piglets and rats. 2-Methyl-5-HT and m-chlorophenylbiguanide
concentration-dependently contracted the ferret ileum, whereas they had
no effect in piglets and rats. In ferrets, the 5-HT-induced contraction
was inhibited by methysergide and by ramosetron, but not by ketanserin or
GR113808. Atropine and tetrodotoxin suppressed contractions elicited by
5-HT, 2-methyl-5-HT and m-chlorophenylbiguanide in ferrets, but not that
elicited by 5-methoxytryptamine. In piglets, 5-HT-induced contraction was
inhibited by methysergide and by tetrodotoxin, but not by ketanserin, ramosetron,
GR113808 or atropine. In rats, 5-HT-induced contraction was inhibited by
methysergide and by ketanserin, but not by ramosetron or tetrodotoxin. In
contrast, GR113808 enhanced contractions elicited by 5-HT or 5-methoxytryptamine.
These results suggest that 5-HT-induced contraction in ferrets is mediated
via 5-HT1 receptors on the muscle and by release of acetylcholine via 5-HT3
receptors. In piglets, 5-HT-induced contraction appears to be mediated by
release of neurotransmitters other than acetylcholine via 5-HT1 receptors.
5-HT-induced contraction in rats is evoked via 5-HT1 and 5-HT2 receptors
on the muscle. Furthermore, 5-HT4 receptors may participate in the relaxation
elicited by 5-HT in rats.
Keywords: Species difference, 5-HT receptor, Distal ileum, Longitudinal
muscle