Lepor H, Shapiro E
J Urol. 1984 Dec;132(6):1226-9. doi: 10.1016/s0022-5347(17)50110-x.
Bladder outlet obstruction in men with benign prostatic hyperplasia is decreased following administration of prazosin, a selective alpha1 adrenergic antagonist. Prazosin presumably binds and antagonizes alpha1 adrenergic receptors on the smooth muscle cells of the prostatic adenoma. This study represents the first identification and characterization of alpha1 adrenergic receptors in the prostate using radioligand receptor binding methods. The binding of [3H] prazosin in homogenates obtained from human prostatic adenomas was saturable and a single high affinity prazosin binding site was identified (Kd = 0.29 +/- 0.09 nM). The alpha1 adrenergic receptor concentration in these homogenates ranged between 0.28 to 2.05 fmol./ mg. wet wt. prostate. The equilibrium dissociation constant and density of prazosin binding sites were similar in different regions of an enucleated prostate suggesting homogeneity of receptor density and receptor binding sites within an adenoma. The receptor density was not directly proportional to the weight of the surgically removed adenoma. The pharmacology of the prazosin binding sites was characterized by competitive binding experiments using [3H] prazosin and several unlabelled adrenergic analogs. The IC50's determined from competitive binding experiments using [3H] prazosin and alpha-methylnorepinephrine, rauwolscine and corynanthine were characteristic of alpha1 adrenergic receptor binding.
给予选择性α1肾上腺素能拮抗剂哌唑嗪后，良性前列腺增生男性的膀胱出口梗阻情况会减轻。哌唑嗪可能与前列腺腺瘤平滑肌细胞上的α1肾上腺素能受体结合并拮抗其作用。本研究首次运用放射性配体受体结合方法对前列腺中的α1肾上腺素能受体进行了鉴定和表征。从人前列腺腺瘤获得的匀浆中，[3H]哌唑嗪的结合具有饱和性，且鉴定出了一个单一的高亲和力哌唑嗪结合位点（解离常数Kd = 0.29 +/- 0.09 nM）。这些匀浆中α1肾上腺素能受体浓度在0.28至2.05 fmol./mg湿重前列腺之间。在摘除的前列腺的不同区域，哌唑嗪结合位点的平衡解离常数和密度相似，表明腺瘤内受体密度和受体结合位点具有同质性。受体密度与手术切除腺瘤的重量不成正比。通过使用[3H]哌唑嗪和几种未标记的肾上腺素能类似物进行竞争性结合实验，对哌唑嗪结合位点的药理学特性进行了表征。使用[3H]哌唑嗪与α-甲基去甲肾上腺素、育亨宾和柯楠因进行竞争性结合实验所确定的半数抑制浓度（IC50）具有α1肾上腺素能受体结合的特征。
