THE EFFECT OF A 5-HT3-ANTAGONIST ON THE ILEAL BRAKE MECHANISM IN THE RAT

Studies have been carried out on 7 male adult rats to investigate how the action of the selective 5-HT3 receptor antagonist, granisetron, influences gastrointestinal transit under control conditions and when it is delayed by ileal infusion of lipid. Stomach to caecum transit time (SCTT) was measured using environmental hydrogen analysis. Subcutaneous administration of granisetron (BRL 43694, 40-mu-g kg-1) significantly delayed the passage of the head of the baked bean meal through the stomach and the small intestine under control conditions (P < 0.05). The same compound, however, significantly reversed the delay in SCTT induced by ileal infusion of lipid (P < 0.001). These apparently paradoxical results may be rationalized by postulating inhibition of receptors on afferent nerves initiating reflexes that both accelerate and delay transit.