Comparative Studies With 5-Hydroxytryptamine and Its Derivatives in Isolated, Blood-Perfused Small Intestine and Tleum Strip of the Rat

Abstract

Abstract--The mode of actions of' 5-hydroxytryptamine (5-HT) and its derivatives, tryptophan (14)), 5-hydroxytryptophan (5-HTP) and 5-hydroxyindole acetic acid(5-HIAA) vas studied on the isolated, blood-perfused small intestine and isolated ileum strip of rats.In the isolated, blood-perfused intestinal preparations, 5-HT and 5-HTP injected into the superior mesenteric artery caused a monophasic fast contraction, while TP and 5-HIAA had no effects on the intestine. The contractile responses to 5-HT and 5-HTP were abolished by tetrodotoxin (TTX), hexamethoitium (C5) and morphine, but were resistant to blockade of either atropine, methvsergidc or phentolamine.On the other hand, in the ileum strip preparations, 5-HT contracted the ileum, but its derivatives had no effects on the ileum. TTX, C,;, morphine and atropine failed to prevent the contractile response to 5-HT, whereas methysergide effectively antagonized the response. The present results indicate that 5-HT acts by exciting intramural neuronal elements or by directly contracting the smooth muscle of the intestine.5-HTP seems to act in the same manner as 5-HT.5-Hydroxytryptamine (5-HT) has been shown to contract smooth muscle of the isolated intestine by a direct action on the muscle fibres or by an indirect effect through excita tion of the intrinsic network of nerves (1-5). These findings, however, were obtained in isolated intestinal preparations bathed in physiological salt solutions. In view of this, it was considered that recordings of response of the intestinal smooth muscle with an intact blood supply may reveal features of the intestinal musculature.In the present experiments, we perfused the isolated small intestine of the rat through the superior mesenteric artery with blood from a donor, using a cross-circulation technique. This method enabled injection of drugs into the superior mesenteric artery and We could observe simultaneously vascular and muscular responses of the intestine.Our objective herein was to determine whether comparable information about the actions of 5-HT and its derivatives could he obtained from isolated, blood-perfused small intestine and from isolated ileum strips of the rat. MA I"ERIALS AND M1 THODSMale Sprague-Dawley rats were used.Isolated, 1,/crcnl perJuse~l.enrall intestinc: Donor rats (550-750 g) were anesthetized with pentobarbital sodium (65 mg/kg i.p.). The animal was placed on a table maintained by a

Effects of Intra-Arterial Bradykinin and Substance P on Isolated, Blood-Perfused Small Intestine of the Rat

“…Lack of any blocking effects of these antagonists suggests that neurons subserving as the final common pathway to the ileal smooth muscle cells probably are not cholinergic, histaminergic or tryptaminergic. Also, catecholamines produce primarily only an ileal relaxation in the same sort of preparations (13). Experiments carried out on isolated muscle strip preparations of the ileum and the taenia coli of the guinea pig or the rat uterus have shown that bradykinin has only a direct action on smooth muscle (3)(4)(5)15).…”

“…The operative and perfusion procedures were as previously described (13). Recipient rats (about 150 g) were deprived of food overnight before the experiment but water was allowed ad libituin.…”

“…Most workers have used isolated smooth muscle preparations bathed in physiological salt solutions. In a previous study (13), a difference was noted in the mode of action of 5-hydroxytryptamine (5-HT) between the isolated blood-perfused small intestinal preparation of the rat and rat isolated ileal strips bathed in a physiological salt solution; the action of 5-HT given intra-arterially to the blood-perfused intestinal preparation was primarily one which stimulated the local neuronal elements, while that of 5-HT applied to isolated ileal strips bathed in physiological salt solution was exerted on ileal smooth muscle. The mode of action of bradykinin and substance P on the ileal region was studied herein using the blood-perfused small intestine of the rat.…”

A Pharmacological Analysis of the Contractile Action of Histamine Upon the Ileal Region of the Isolated, Blood‐perfused Small Intestine of the Rat

“…However, these studies were carried out on isolated muscle strip preparations bathed in physiological salt solutions. Recently, attempts were made to perfuse the rat isolated small intestine through the superior mesenteric artery with arterial blood from a donor rat and to record the intestinal muscle tone (Sakai, Akima & Shiraki, 1979). The study revealed certain differences in the mode of action of 5-hydroxytryptamine between the isolated blood-perfused intestinal preparation of the rat and rat isolated ileal strip bathed in physiological salt solution ; the action of 5-HT injected intra-arterially to the bloodperfused intestinal preparation was primarily to stimulate neuronal elements there, while that of 5-HT given to isolated ileal strips bathed in physiological salt solution was exerted on ileal smooth muscle.…”