The effect and mechanism of the prokinetic action of cisapride on gastrointestinal smooth muscle

Hon Tsu Chen, Mooi Hun Goh, Shiann Pan

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Cisapride is a new prokinetic agent which can facilitate or restore motility throughout the entire gastrointestinal tract. Although facilitation of acetylcholine release has been suggested, the mechanism of action of cisapride is not clear. To investigate the effect and mechanism of action of cisapride, we used isolated muscle strips (with mucosa and submucosa removed) of guinea pig antrum, ileum and colon to study: (1) the dose response to cisapride, (2) the effect of antagonists (atropine and tetrodotoxin) on the stimulatory effect of cisapride. Besides these studies, we also used 3 H-acetylcholine release method to investigate the acetylcholine release effect of cisapride. Cisapride elicited a dose-related enhancement of baseline activity (motility index) on the antrum and contraction on the ileum and colon at the dose of 4, 40 and 400 nM. At higher doses (4 μM) cisapride caused inhibition. This bell-shaped dose response curve suggested that cisapride might be autoinhibitory or that the receptors of cisapride might consist of high affinity stimulatory and low affinity inhibitory sites. The stimulatory responses elicited by cisapride (400 nM) were not significantly inhibited by atropine and tetrodotoxin in the antrum, ileum and colon. This suggested that cisapride might act directly on the smooth muscle. Cisapride (400 nM) evoked a rather small increase of 3 H-acetylcholine release on the antrum, ileum and colon. Because the percentage of increase was small and we had demonstrated that the stimulatory effects of cisapride were not blocked by atropine and tetrodotoxin, the acetylcholine release effect of cisapride was considered unimportant.
頁(從 - 到)218-223
期刊Gastroenterologia Japonica
出版狀態已發佈 - 4月 1993

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