title: Actions of the alpha-1 adrenoceptor blocker bunazosin on the norepinephrine-induced contraction of smooth muscles in the rabbit proximal urethra.
abstract: Effects of bunazosin on the norepinephrine-induced electrical and mechanical activities of smooth muscles of the rabbit proximal urethra were investigated using microelectrode and tension recording methods. Responses to norepinephrine were mediated by activation of both alpha-1 and beta adrenoceptors. In the presence of propranolol, the norepinephrine-induced contraction increased and, with yohimbine, the phasic but not tonic contraction was only inhibited slightly. Contributions of the alpha-2 adrenoceptor to the norepinephrine-induced contraction were negligible. Bunazosin inhibited in a concentration-dependent manner both the phasic and tonic responses of the norepinephrine-induced contraction, and the concentration-response relationship for norepinephrine shifted to the right. The Schild plot obtained from measurements of tonic responses in this antagonism yielded a straight line with a slope of 0.96. The pA2 value for bunazosin was 8.39 and the KB value was 4.1 nM. Prazosin had similar effects (the corresponding values being 0.96, 8.21 and 6.2 nM, respectively). The mechanical response evoked by field stimulation was composed of cholinergic, noradrenergic alpha-1 and noncholinergic-nonadrenergic contractions and of a subsequent nonadrenergic-noncholinergic relaxation. Bunazosin inhibited the twitch contraction evoked by field stimulation more than did prazosin, albeit not completely. These results indicate that although the smooth muscle tone in the urethra is regulated by multiple neural factors, the elevation of the tone is regulated predominantly by activation of the alpha-1 adrenoceptors. Bunazosin has an antagonistic action on this receptor. The actions of bunazosin are discussed in relation to the clinical application in cases of inadequate micturition.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D014521:Urethra / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C018176:bunazosin; D011433:Propranolol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D006145:Guanethidine