EFFECTS OF ONDANSETRON ON ELECTRICALLY-EVOKED CONTRACTION IN RAT STOMACH FUNDUS - POSSIBLE INVOLVEMENT OF 5-HT2B RECEPTORS

This study examined the effects of ondansetron, an antagonist of the 5 -hydroxytryptamine (5-HT3) receptor without 5-HT4 receptor agonistic a ctivity, on electrically evoked contractions and acetylcholine release in rat stomach fundus strips. Ondansetron (10(-8)-10(-4) M) produced a concentration-dependent increase in the magnitude of the electricall y evoked contraction, while it inhibited the release of acetylcholine induced by electrical field stimulation. The stimulatory effect of ond ansetron (10(-6) M) on electrically evoked contractions was antagonize d by yohimbine, a 5-HT2B receptor antagonist, but not by SDZ 205-557 ( 2-methoxy-4-amino-5-chloro-benzoic acid 2-[diethylamino] ethyl ester), a 5-HT4 receptor antagonist. In the presence of tetrodotoxin, ondanse tron (10(-7)-10(-5) M) enhanced the contractions induced by acetylchol ine. This stimulatory effect of ondansetron on acetylcholine-induced c ontractions was antagonized by yohimbine. These data suggest that onda nsetron potentiates the contractile response to acetylcholine in the r at stomach fundus through the activation of 5-HT2B receptors. (C) 1997 Elsevier Science B.V.