Abstract

The effects of 5-hydroxytryptamine (5-HT), the 5-HT1-like receptor agonist 5-carboxamidotryptamine and the 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine were studied on circular muscle strips of the canine terminal ileum and ileocolonic junction. Serial administration of 5-HT or of 5-carboxamidotryptamine induced slow tonic contractions that at higher concentrations of 5-HT (10(-4)-3 x 10(-4] were preceded by an initial relaxation and a fast phasic contraction. The concentration-response curves to both agonists were competitively shifted to the right by the mixed 5-HT1/5-HT2 receptor antagonist methysergide. The initial relaxation and fast phasic contraction were inhibited by the 5-HT3 receptor antagonist ICS 205-930 and tetrodotoxin. Atropine blocked the fast phasic contraction, but enhanced the relaxation. During acetylcholine-induced contractions, 5-HT and 2-methyl-5-hydroxytryptamine (greater than or equal to 10(-5) M), but not 5-carboxamidotryptamine, evoked relaxations that were blocked by ICS 205-930 and tetrodotoxin, but not by adrenoceptor antagonists. Thus, in the canine terminal ileum and ileocolonic junction, 5-HT stimulates neuronal 5-HT3 receptors and excitatory 5-HT1-like receptors located on smooth muscle. Stimulation of the 5-HT3 receptors results in an acetylcholine-mediated contraction and a relaxation mediated by an as yet unknown nonadrenergic noncholinergic neurotransmitter.