Abstract
Abstract
Isolated guinea pig ileal longitudinal muscle was stimulated transmurally with a frequency of 0.1 Hz, duration of 0.5 msec, and supramaximal voltage (80-100 V). Transmural stimulation induces ileal contractions via activation of cholinergic neurons. α2-Adrenergic agonists block the response to transmural stimulation via activation of prejunctional α2 receptors which inhibit release of acetylcholine from cholinergic nerve terminals. Urapidil has been reported to have α2-agonistic actions, and therefore was compared to the prototypic α2 agonists, clonidine and B-HT 920. Clonidine and B-HT 920 depressed responses to transmural stimulation in the guinea pig ileum. Clonidine was the most potent inhibitor of the contractions, followed closely by B-HT 920. Very high concentrations of urapidil were necessary to suppress nerve-induced contractions of the ileum. The effects of clonidine and B-HT 920, but not urapidil, were antagonized by the selective α2 antagonist, yohimbine. In unstimulated preparations, in which exogenous acetylcholine was used to elicit contractions of the ileum, urapidil depressed the response while clonidine and B-HT 920 had no effect. When PGF1α was used to contract the ileum, no inhibitory effects were noted for urapidil, clonidine, or B-HT 920. Therefore urapidil, only in high concentrations, inhibits the contraction to transmural stimulation by depressing the response at a postjunctional cholinergic site. No evidence was found that urapidil can act as an agonist at a prejunctional α2-receptor site.
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