Purpose: We investigated the presence and functional role of beta-adrenoceptor subtypes in the bladder base and proximal urethra of the female pig.
Materials and methods: Saturation experiments were done with 7 concentrations (0.25 to 16 nM.) of [(3)H]-dihydroalprenolol (NEN Life Science Products, Boston, Massachusetts). Competition experiments with [(3)H]-dihydroalprenolol were performed with unlabeled antagonists (beta1 selective CGP20712A, beta2 selective ICI118551 and beta3 selective SR59230A). In functional studies concentration-relaxation curves to the beta3-agonist BRL37344 were obtained and antagonist affinities for SR59230A were determined.
Results: CGP20712A displaced [(3)H]-dihydroalprenolol with low affinity, suggesting that beta1-adrenoceptors were not present. Displacement with ICI118551 in the bladder base and urethra best fitted a 2-site model with 20% and 28% high affinity sites (beta2), respectively. Displacement experiments with SR59230A in the bladder base demonstrated that 59% of binding sites had high affinity (beta3). In the urethra displacement with SR59230A best fitted a 1-site model but with a pK(i) of 7.2 that was intermediate between that expected for beta2 and beta3-adrenoceptors. In functional studies BRL37344 induced relaxation with pEC50 values of 5.5 and 8, and a maximum relaxation response relative to 30 microM. isoprenaline of 79% and 90% in the bladder base and urethra, respectively. The affinity value of SR59230A for the response to BRL37344 was 7.87 and 7.71 in the bladder base and urethra, respectively, which were intermediate between those of beta2 and beta3-adrenoceptors.
Conclusions: Apparently beta3-adrenoceptors are the predominant beta-adrenoceptor subtype present in the lower urinary tract of the pig.