The role of β3‐adrenoceptors in mediating relaxation of porcine detrusor muscle

Open Access
Publisher Website
Google Scholar
Abstract
β‐adrenoceptors mediate relaxation of bladder detrusor smooth muscle. This study investigates the contribution of β3‐adrenoceptors to relaxation of the pig urinary bladder. Cell membranes were prepared from detrusor muscle of the pig bladder dome and competition experiments with [3H]‐dihydroalprenolol (DHA), a non‐selective β‐adrenoceptor antagonist was used as a specific radioligand to determine the presence of β‐adrenoceptor subtypes. In functional experiments, isolated detrusor muscle strips were used to determine the potency of agonists and the affinity of antagonists. In competition binding experiments, CGP20712A (β1‐adrenoceptor selective) displaced [3H]‐DHA from a single binding site with a low affinity. In contrast, displacement data for ICI 118551 (β2‐adrenoceptor antagonist) and SR59230A (β3‐adrenoceptor antagonist) best fitted a two‐site model suggesting a predominant (70%) population of β3‐adrenoceptors. In functional studies, isoprenaline and salbutamol (β2‐adrenoceptor agonist) relaxed KCl precontracted muscle strips with high potency (pEC507.7 and 7.2, respectively), whilst CGP12177 and BRL37344 (β3‐adrenoceptor agonists) had low potency and were partial agonists. CGP20712A and atenolol (β1‐adrenoceptor antagonists) antagonised responses with a low affinity. ICI118551 antagonized responses to isoprenaline and salbutamol with a high affinity (pKB=7.8 and 8.7, respectively), but the Schild slopes were low suggesting that responses were mediated by more than one β‐adrenoceptor. The Schild plot for SR59230A was biphasic, apparent pKBvalues for 3 – 10 nMSR59230A being 8.6 and those for 30 nM – 1 μMbeing 7.7. These data suggest that β3‐adrenoceptors are the predominant β‐adrenoceptor subtype present in the pig bladder and that β‐adrenoceptor mediated responses of this tissue are mediatedviaboth the β2‐ and β3‐adrenoceptor subtypes. British Journal of Pharmacology(2002)135, 129–134; doi:10.1038/sj.bjp.0704470