The Functional Role of β-Adrenoceptor Subtypes in Mediating Relaxation of Pig Urethral Smooth Muscle

Abstract

The predominant beta-adrenoceptor subtype present in the bladder and urethra is beta3-adrenoceptors. We investigated the role of beta-adrenoceptors in mediating relaxation of the in vitro female pig urethra. Circular strips of urethral tissues were pre-contracted with KCl. Concentration-relaxation curves (CRCs) to beta-adrenoceptor agonists were obtained in the absence and presence of antagonists. The nonselective beta-agonist isoproterenol in 30 animals and the beta3-adrenoceptor agonist BRL37344 in 4 relaxed with high potency (pEC50 7.2 and 8.1, respectively), while the beta2-adrenoceptor agonist salbutamol in 6 had low potency (pEC50 6.1). Mean maximal relaxation responses of BRL37344 and salbutamol relative to maximal isoproterenol responses were 89.8% and 76.7%, respectively. Propranolol (10 to 100 nM) in 18 animals antagonized CRCs to isoproterenol with high affinity (apparent pKB 8.6) but the Schild plot had a slope that was significantly less than unity (0.68, p <0.01). High concentrations of the beta1-antagonist CGP20712A (3 to 30 microM) in 12 animals had no effect on responses to isoproterenol. The beta2-antagonist ICI118551 (30 to 300 nM) in 25 animals antagonized responses to isoproterenol with high affinity (apparent pKB 8.03) with a Schild slope not different from unity (0.79). The beta3-antagonist SR59230A (10 to 100 nM) in 12 animals antagonized CRCs to isoproterenol with an apparent pKB of 7 and with a Schild slope that was again significantly less than unity (0.62, p <0.01), indicating that responses to isoproterenol are mediated by more than 1 beta-adrenoceptor subtype. According to the Schild plot of unity ICI118551 (3 to 30 nM) in 18 animals competitively antagonized responses to salbutamol with high affinity (pA2 8.5). In the pig urethra beta-adrenoceptor mediated relaxations to isoproterenol are mediated via beta2 and beta3-adrenoceptors, while responses to beta2-adrenoceptor agonists such as salbutamol appear to be mediated only via beta2-adrenoceptors.