Ascending contraction mediated by 5-hydroxytryptamine3 receptors in canine small intestine

We investigated the mechanism of ascending contraction induced by activation of 5-hydroxytryptamine3 (5-HT3) receptors in anesthetized dogs. Pressure-measuring balloons were inserted into a loop of extrinsically denervated jejunum. Drugs were administered via the arterial tree to the oral or the anal segment and the ensuing mechanical responses were monitored. Administration of 2-methyl-5-HT (440 pmol-44 nmol) to the anal segment caused contractions in the oral segment in a dose-dependent manner. This response was inhibited by treating the anal segment with ICS 205-930, cocaine, hexamethonium, or tetrodotoxin and by treating the oral segment with atropine or hexamethonium. The response persisted even after abolition of contraction in the anal segment by nifedipine. These results imply that activation of 5-HT3 receptors can induce an ascending contraction through an enteric excitatory pathway formed by a series of cholinergic interneurons and final cholinergic motor neurons, apart from the anal contraction.