Inhibition of the effect of serotonin on rat ileal transport by cisapride: evidence in favour of the involvement of 5-HT2 receptors.

K J Moriarty, N B Higgs, M Woodford, G Warhurst, L A Turnberg

Department of Medicine, Hope Hospital (University of Manchester School of Medicine), Salford.

Cisapride is a synthetic drug which binds, in vitro, to type 2 serotonin receptors. We examined the influence of serotonin and cisapride on ion transport across intestinal mucosa in vitro and studied the effect of cisapride on the response to serotonin. Segments of ileum of male Sprague-Dawley rats were stripped of muscle layers and mounted in flux chambers. The addition of serotonin (10(-8) to 10(-4) M) to the serosal aspect of the mucosa caused a rapid, dose-dependent rise in short circuit current and transmural potential difference. Cisapride alone (5 X 10(-5) M), when added to the mucosal and serosal surfaces, had no effect on the short circuit current, transmural potential difference, resistance, or sodium and chloride fluxes across the mucosa. It did, however, inhibit the response of the mucosa to serotonin (10(-5) M) in a dose dependent manner and blocked it completely at a concentration of 5 X 10(-5) M. Serotonin (5 X 10(-5) M) increased serosal to mucosal flux of chloride from 12.6 +/- 0.8 to 15.2 +/- 0.6 mumol/cm2/h (p less than 0.025), thus reducing net chloride absorption from 4.65 +/- 0.81 to 1.49 +/- 1.04 mumol/cm2/h (p less than 0.05). This effect was completely blocked by cisapride (5 X 10(-5) M). In summary, cisapride inhibits the effect of serotonin on rat ileal ion transport, probably by blocking type 2 serotonin receptors.

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