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  • Title: Relaxation of human detrusor muscle by selective beta-2 and beta-3 agonists and endogenous catecholamines.
    Author: Badawi JK, Seja T, Uecelehan H, Honeck P, Kwon ST, Bross S, Langbein S.
    Journal: Urology; 2007 Apr; 69(4):785-90. PubMed ID: 17445682.
    Abstract:
    OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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