Inhibition oftheeffect ofserotonin on ratileal transport bycisapride: evidence infavour ofthe involvement of5-HT2 receptors

SUMMARY Cisapride is a synthetic drugwhichbinds, in vitro, to type 2serotonin receptors. Weexaminedtheinfluenceofserotoninandcisapride on ion transport across intestinal mucosa invitroand studied the effect of cisapride on the response to serotonin. Segments of ileum of maleSprague-Dawley rats were strippedofmusclelayersandmountedinfluxchambers.Theadditionofserotonin(10-1to10-4M) to theserosal aspect ofthe mucosa caused a rapid,dose-dependentriseinshortcircuit current andtransmuralpotentialdifference. Cisapridealone(5 x 10-5M),whenadded to themucosalandserosalsurfaces,had no effect on theshortcircuit current, transmuralpotentialdifference,resistance, or sodiumandchloridefluxes across the mucosa. Itdid,however,inhibitthe response of the mucosa to serotonin (10-5M) in a dose dependent manner and blocked itcompletely at a concentrationof5 x 10-5M. Serotonin(5 10-5M)increasedserosal to mucosalfluxof chloride from 12-6±0*8 to 15*2±0-6 fimol/cm2/h (p<0025), thus reducing net chlorideabsorption from 4*65±0-81