The effects and selectivity of β-adrenoceptor agonists in rat myometrium and urinary bladder

Recent evidence supports a role for β3-adrenoceptors in human non-pregnant and pregnant myometrium. The present study was designed to characterize the pharmacology of β-adrenoceptors involved in the function of non-pregnant rat myometrium by comparison of the activity of several β-adrenoceptor agonists and antagonists in isolated rat uterus and urinary bladder. Contractions of myometrial and detrusor strips were induced by adding 1 nM oxytocin and 15 mM KCl respectively. Cumulative concentration-response curves to the selective β3-adrenoceptor agonists, CL 316243 and BRL 37344 and the selective β2-adrenoceptor agonist ritodrine were obtained in the presence and absence of the selective β2-adrenoceptor antagonist ICI 118551 and the non-selective β-adrenoceptor antagonist bupranolol. Both BRL 37344 (pD2 = 6.79 ± 0.09) and ritodrine (pD2 = 6.89 ± 0.19) produced potent inhibition of oxytocin-induced contractions in myometrial strips; CL 316243 was inactive at concentrations up to 10 μM. Concentration effect curves to both BRL 37344 and ritodrine were shifted (10 to 30-fold) to the right in the presence of ICI 118551 (10 nM). BRL 37344 (pD2 = 8.51 ± 0.21) and CL 316243 (pD2 = 8.61 ± 0.24) produced potent inhibition of detrusor strips, while ritodrine was almost 100-fold less potent (pD2 = 5.83 ± 0.17). The response to all agonists was significantly attenuated by pretreatment with bupranolol (10 μM), but only ritodrine was affected by ICI 118551 (1 μM). These results demonstrate that relaxation of rat myometrium is mediated by β2-adrenoceptors while, consistent with previous reports, the β3-subtype is primarily responsible for relaxation of rat detrusor.