Granisetron and ondansetron: effects on the ileal brake mechanism in the rat

Studies were carried out on 20 male adult rats to investigate how the action of the selective 5-HT3-receptor antagonists, granisetron and ondansetron, influence gastrointestinal transit under control conditions and when stomach-to-caecum transit was 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, 80 or 150 micrograms 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). Similarly, subcutaneous administration of ondansetron (GR 38032F, 80 or 150 micrograms kg-1) delayed control SCTT of the head of the meal but this did not reach statistical significance. In contrast, granisetron significantly reversed the delay in SCTT induced by ileal infusion of lipid at 40 (P < 0.001), 80 (P < 0.01) and 150 micrograms kg-1 (P < 0.05). Ondansetron also reversed the lipid-induced delay at 40 (P < 0.01), 80 (P < 0.001) and 150 micrograms kg-1 (P < 0.001). These apparently conflicting results may be rationalized by postulating the presence of 5-HT3 receptors on afferent nerves which, when inhibited by the specific antagonists, initiate reflexes that both accelerate and delay transit.