Badawi Jasmin Katrin, Seja Tobias, Uecelehan Hatice, Honeck Patrick, Kwon Sun-Tscheol, Bross Stephan, Langbein Sigrun
Department of Urology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
Urology. 2007 Apr;69(4):785-90. doi: 10.1016/j.urology.2007.01.059.
The goal of this study was to identify potent relaxant agents of the human detrusor muscle. Therefore, the relaxant effects of different selective beta (beta)-adrenoceptor agonists were examined. Also, the relaxant effects of the endogenous catecholamines were investigated to functionally characterize the beta-adrenoceptor subtype mainly responsible for adrenergic-mediated relaxation in the detrusor muscle of humans.
Experiments were performed on muscle strips of human detrusor suspended in a tissue bath. The tissue originated from patients who had undergone total cystectomy. The selective beta3-agonists BRL 37344, ZD 7114, and CGP 12177, the selective beta2-agonists terbutaline and clenbuterol, and the nonselective beta-agonist isoprenaline were investigated. Concentration-relaxation curves of the catecholamines were performed to determine the rank order of potency.
The maximal relaxation induced by BRL 37344, ZD 7114, and CGP 12177 was 36%, 39%, and 37%, respectively. The corresponding pD2 values were 6.73, 4.82, and 6.09, respectively. Terbutaline and clenbuterol induced a maximal relaxation of 48% and 27%, and their pD2 value was 4.97 and 5.34, respectively. Isoprenaline, adrenaline, and noradrenaline induced a maximal relaxation of 72%, 58%, and 79%, respectively. The corresponding pD2 values were 6.18, 6.16, and 6.09, respectively. Because their differences were not significant, no rank order of potency was determined.
Beta-adrenergic agonists are potent relaxant agents of the human detrusor muscle in vitro. Both beta2 and beta3-adrenoceptors contribute to adrenergic-mediated relaxation. Our results point to a slightly greater role for the beta3-receptor in human detrusor muscle.
本研究的目的是确定对人逼尿肌有强效松弛作用的药物。因此，研究了不同选择性β（β）-肾上腺素能受体激动剂的松弛作用。此外，还研究了内源性儿茶酚胺的松弛作用，以从功能上鉴定主要负责介导人逼尿肌肾上腺素能介导的松弛作用的β-肾上腺素能受体亚型。
在置于组织浴中的人逼尿肌肌条上进行实验。组织取自接受全膀胱切除术的患者。研究了选择性β3-激动剂BRL 37344、ZD 7114和CGP 12177、选择性β2-激动剂特布他林和克伦特罗以及非选择性β-激动剂异丙肾上腺素。绘制儿茶酚胺的浓度-松弛曲线以确定效价顺序。
BRL 37344、ZD 7114和CGP 12177诱导的最大松弛率分别为36%、39%和37%。相应的pD2值分别为6.73、4.82和6.09。特布他林和克伦特罗诱导的最大松弛率分别为48%和27%，其pD2值分别为4.97和5.34。异丙肾上腺素、肾上腺素和去甲肾上腺素诱导的最大松弛率分别为72%、58%和79%。相应的pD2值分别为6.18、6.16和6.09。由于它们之间的差异不显著，因此未确定效价顺序。
β-肾上腺素能激动剂在体外是人逼尿肌的强效松弛剂。β2和β3-肾上腺素能受体均参与肾上腺素能介导的松弛作用。我们的结果表明β3-受体在人逼尿肌中的作用略大。
