Relaxant effects of beta-adrenergic agonists on porcine and human detrusor muscle.
OBJECTIVE
Relaxant effects of different beta-adrenoceptor agonists on porcine and human detrusor were examined. Thus, the beta-adrenoceptor subtype mainly responsible for relaxation in the detrusor muscle of pigs was characterized. Additionally, different effects of several beta-agonists in both species were shown.


METHODS
Experiments were performed on muscle strips of porcine and human detrusor suspended in a tissue bath. The relaxant effects of the non-selective beta-agonist isoprenaline, the selective beta2-agonists procaterol, salbutamol and the selective beta3-agonists BRL 37344, CL 316 243 and CGP 12177 on potassium-induced contraction were investigated. The inhibitory effect of different substances on the maximum contraction and the rank order of potency for endogenous catecholamines was determined in pigs. Furthermore, concentration-relaxation curves were performed for pigs and humans.


RESULTS
Pigs: In the pre-treatment experiments isoprenaline and procaterol showed similar effects. The concentration-response experiments showed that the maximum relaxation induced by procaterol and salbutamol was more than 90%, not significantly different from isoprenaline, whereas the maximum relaxations of CL 316 243, BRL 37344 and CGP 12177 amounted to 68, 70 or 30%, respectively. Rank order of potencies was isoprenaline > or = adrenaline > noradrenaline. Humans: Isoprenaline, procaterol, salbutamol and CL 316 243 showed a maximum relaxation of 80, 41, 24 and 35% and pD2 values of 6.24, 5.65, 5.48 and 5.55, respectively.


CONCLUSIONS
Beta2-receptors play a main functional role in mediating relaxation of porcine detrusor. Selective beta2- and beta3-agonists similarly relax the human detrusor. Effects were smaller compared with the pig.
Badawi
J K
JK
Department of Urology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany. jasmin-katrin.badawi@uro.ma.uni0heidelberg.de
Uecelehan
H
H
Hatzinger
M
M
Michel
M S
MS
Haferkamp
A
A
Bross
S
S
D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology*; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D013552:Swine
D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D004983:Ethanolamines; D011412:Propanolamines; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C057368:BRL 37344; D007545:Isoproterenol; D000420:Albuterol; C033394:CGP 12177; D009638:Norepinephrine; D017265:Procaterol; D004837:Epinephrine