5-HT-induced jejunal motor activity: Enteric locus of action and receptor subtypes

The role of 5-hydroxytryptamine (5-HT), its enteric locus of action, and receptor subtypes involved in the regulation of jejunal contractions were investigated by close intra-arterial infusions in conscious dogs. Close intra-arterial infusions of 5-HT in short segments of the jejunum stimulated phasic contractions that were blocked completely by atropine, partially by tetrodotoxin, and not affected by hexamethonium. This response was also blocked significantly by 5-HT(2A) and 5-HT(2C) receptor antagonists but was not affected by 5-HT(1A)/5-HT(1B), 5-HT₃, and 5-HT₄ receptor antagonists. Spontaneous phase III contractions were inhibited significantly by 5-HT(2A) and 5-HT(2C) receptor antagonists, not affected by 5-HT(1A)/5-HT(1B) and 5- HT₃ receptor antagonists, and enhanced by 5-HT₄ receptor antagonists. Repeated close intra-arterial infusions of 5-HT over several days stimulated giant migrating contractions. We conclude that in the conscious state, 5-HT acts on 5-HT(2A) and 5-HT(2C) receptors located on postsynaptic cholinergic neurons in the canine jejunum to stimulate phasic contractions and phase III activity. The 5-HT₄ receptors in the canine small intestine may be localized on nonadrenergic, noncholinergic inhibitory neurons; these receptors suppress the amplitude and duration of phase III activity.