Relaxation of human detrusor muscle by selective beta-2 and beta-3 agonists and endogenous catecholamines.
OBJECTIVE
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.
Badawi
Jasmin Katrin
JK
Department of Urology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany. jasmin-katrin.badawi@lycos.de
Seja
Tobias
T
Uecelehan
Hatice
H
Honeck
Patrick
P
Kwon
Sun-Tscheol
ST
Bross
Stephan
S
Langbein
Sigrun
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000368:Aged; D002395:Catecholamines / Q000494:pharmacology*; D002976:Clenbuterol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D010642:Phenoxyacetates / Q000494:pharmacology; D050198:Phenoxypropanolamines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D004983:Ethanolamines; D010642:Phenoxyacetates; D050198:Phenoxypropanolamines; D011412:Propanolamines; C071909:ICI D7114; C057368:BRL 37344; D007545:Isoproterenol; D013726:Terbutaline; C033394:CGP 12177; D002976:Clenbuterol