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