In vitro characterization of .ALPHA.-adrenergic receptor in rabbit detrusor muscle.

Abstract

Abstract-In the isolated detrusor smooth muscle of the rabbit urinary bladder, acetylcholine, prostaglandin (PG) F2a, histamine and methoxamine produced dose-dependent contractions. The order of efficacy was acetylcholine>PGF2a> histamine>methoxamine.Acetylcholine and oxotremorine increased tension remarkably in the rabbit detrusor muscle; and McN-A-343 also developed tension, but with weaker sensitivity and efficacy. The contractile response to acetylcholine was competitively antagonized by atropine (pA2 9.24) and pirenzepine (pA2 6.96), respectively. Histamine and 2-pyridylethylamine caused dose-dependent contractions. On the other hand, dimaprit caused no response in this tissue. Mepyramine (pA2 8.80) competitively antagonized the contraction induced by histamine, whereas cimetidine failed to antagonize the contraction even at a high concentration of 10-5 M. Norepinephrine, phenylephrine and methoxamine have greater efficacies in the ability to contract than clonidine. R(-) and S(+)-YM 12617 and YM-12617 (pA2 10.4, 8.31 and 9.75, respectively) and prazosin (pA2 8.13), phentolamine (pA2 7.55) and yohimbine (pA2 6.44) competitively an tagonized the contraction elicited by methoxamine. These results suggest that the contraction of rabbit detrusor muscle can be mediated by a1-adrenergic receptors as well as M2-muscarinic and H1-histaminergic receptors and suggest that the contractile force mediated by a, -adrenergic receptor agonist i s smaller than those stimulated by the other receptor agonists.