Prejunctional 2-Adrenoceptor Mediated Inhibitory Action of Clonidine and B-HT 920, but Not Urapidil in Guinea Pig lleum

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Abstract
Isolated guinea pig ileal longitudinal muscle was stimulated transmurally with a frequency of 0.1 Hz, duration of 0.5 ms and supramaximal voltage (80-100 V). Transmural stimulation induces ileal contractions via activation of cholinergic neurons. .alpha.2-Adrenergic agonists block the response to transmural stimulation via activation of prejunctional .alpha.2 receptors which inhibit release of acetylcholine from cholinergic nerve terminals. Urapidil was reported to have .alpha.2-agonistic actions and therefore was compared to the prototypic .alpha.2 agonists, clonidine and B-HT 920 [alefexole hydrochloride]. 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 .alpha.2 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 PG[prostaglandin]F1.alpha. was used to contract the ileum, no inhibitory effects were noted for urapidil, clonidine, or B-HT 920. 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 .alpha.2-receptor site.