5-HT-induced colonic contractions: Enteric locus of action and receptor subtypes

The role of 5-hydroxytryptamine (5HT), its enteric locus of action, and the receptor subtypes involved in the stimulation of in vivo phasic contractions in the colon were investigated by close intra-arterial infusions in conscious dogs. The contractile response to 5-HT was blocked completely by prior close intra-arterial infusion of atropine and reduced significantly by prior close intra-arterial infusions of tetrodotoxin and hexamethonium. The contractile response was, however, enhanced by the inhibition of nitric oxide (NO) synthase by a prior close intra-arterial infusion of N(ω)-nitro-L- arginine methyl ester. Prior close intra-arterial infusions of 5-HT(1A)/5- HT(1B), 5-HT(2A), 5-HT(2C), and 5-HT₄ receptor antagonists had no significant effect on the contractile response to 5-HT. By contrast, 5-HT₃ receptor antagonist significantly and dose dependently inhibited the contractile response to 5-HT. We conclude that the in vivo phasic contractile response to 5-HT in the colon is mediated mainly by 5-HT₃ receptors located on pre- and postsynaptic cholinergic enteric neurons. 5-HT receptors may also be localized on nonadrenergic, noncholinergic inhibitory motoneurons that use NO as a neurotransmitter.