Species Differences in the 5-Hydroxytryptamine-Induced Contraction in the Isolated Distal Ileum.

Abstract

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-chloro phenylbiguanide 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 ketan serin, 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 5-Hydroxytryptamine (5-HT) is known to be distri buted in blood platelets, the nervous system and entero chromaffin cells. In the gastrointestinal tract, 5-HT is reported to contribute to the regulation of the motility and secretion via several 5-HT-receptor subtypes. The in volvement of the 5-HT-receptor subtype in 5-HT-induced intestinal contraction has been well-examined in the guinea pig small and large intestines (1-8). In contrast, the effect of 5-HT on the regulation of intestinal motility has not been established in species other than guinea pigs.Defecation and intestinal transit in rats are frequently utilized as an in vivo system for the evaluation of the ac tion of 5-HT on the motility of the small and large intes tine. However, the involvement of 5-HT receptor sub types in 5-HT-elicited responses has been less extensively investigated in vitro by the use of selective 5-HT receptor antagonists in rat isolated intestine. In the present study, we examined the participation of 5-HT1-, 5-HT2-, 5-HT3 and 5-HT4-receptor subtypes in 5-HT-induced contrac tion in rat isolated distal ileum.Since the ferret and piglet have been shown to have similarities with respect to anatomical and physiological characteristics of the gut to that of humans (9, 10), the intestinal responses in ferret and piglet are suggested to be good models of some of the physiologic and pharma cologic processes in humans. Furthermore, 5-HT-con ta...

Interactions of Serotoninergic, Cholinergic, and Tachykinin‐Containing Nerve Elements in the Rabbit Small Intestine

“…Data obtained in rat ileum are rather controversial. Some studies claimed that 5-HT 2A and 5-HT 1 receptors located on the smooth muscle were involved in 5-HT-induced contractions, and neither TTX nor atropin caused inhibition suggesting a direct effect on rat ileal muscle (Briejer et al, 1997;Yamano et al, 1997). Meanwhile, the role of 5-HT 3 receptors acting through neuronal activation in rat ileum was also proved (Chetty et al, 2006).…”

Characteristics of 5-Hydroxytryptamine Receptors Involved in Contraction of Feline Ileal Longitudinal Smooth Muscle

“…5-HT is known to be distributed in blood platelets, the GI tract and the central nervous system (CNS) of animals and humans [1][2][3][4][5]. Approximately 80% of the human body's total 5-HT is located in the enterochromaffin cells in the gut, where it is reported to be involved in intestinal movements via several 5-HT receptor subtypes [3,6].…”

“…A number of studies have characterized 5-HT-induced muscle contraction or relaxation responses and enhanced secretion in the GI tract via a multiplicity of 5-HT receptor subtypes [5,[9][10][11][12][13]. For example, in ferrets, 5-HT1 and 5-HT3 receptors mediate contraction, whereas in piglets, 5-HT1 receptors mediate the contraction in the ileum.…”

“…In addition, 5-HT2 receptors mediate contraction and 5-HT4 receptors mediate relaxation in the rat stomach [11]. 5-HT1 and 5-HT2 receptors mediate contractions and 5-HT4 receptors mediate the relaxation in the ileum [5,12]. In chickens, 5-HT1-and 5-HT2-like receptors mediate the contractions in the ileum [11].…”

“…5-HT4-like receptors mediate the relaxation of human colon [14]. In such studies, guinea-pig, rat, mouse, ferret, chicken and human have been widely used [5,[9][10][11][12][13][14]. However, the effect of 5-HT on the regulation of intestinal contraction or which 5-HT receptor is involved in the 5-HT-elicited response has not been established in isolated feline intestine.…”