The role of beta(3)-adrenoceptors in mediating relaxation of porcine detrusor muscle

Br J Pharmacol. 2002 Jan;135(1):129-34. doi: 10.1038/sj.bjp.0704470.

Abstract

1. beta-adrenoceptors mediate relaxation of bladder detrusor smooth muscle. This study investigates the contribution of beta(3)-adrenoceptors to relaxation of the pig urinary bladder. 2. Cell membranes were prepared from detrusor muscle of the pig bladder dome and competition experiments with [(3)H]-dihydroalprenolol (DHA), a non-selective beta-adrenoceptor antagonist was used as a specific radioligand to determine the presence of beta-adrenoceptor subtypes. In functional experiments, isolated detrusor muscle strips were used to determine the potency of agonists and the affinity of antagonists. 3. In competition binding experiments, CGP20712A (beta(1)-adrenoceptor selective) displaced [(3)H]-DHA from a single binding site with a low affinity. In contrast, displacement data for ICI 118551 (beta(2)-adrenoceptor antagonist) and SR59230A (beta(3)-adrenoceptor antagonist) best fitted a two-site model suggesting a predominant (70%) population of beta(3)-adrenoceptors. 4. In functional studies, isoprenaline and salbutamol (beta(2)-adrenoceptor agonist) relaxed KCl precontracted muscle strips with high potency (pEC(50) 7.7 and 7.2, respectively), whilst CGP12177 and BRL37344 (beta(3)-adrenoceptor agonists) had low potency and were partial agonists. CGP20712A and atenolol (beta(1)-adrenoceptor antagonists) antagonised responses with a low affinity. ICI118551 antagonized responses to isoprenaline and salbutamol with a high affinity (pK(B)=7.8 and 8.7, respectively), but the Schild slopes were low suggesting that responses were mediated by more than one beta-adrenoceptor. The Schild plot for SR59230A was biphasic, apparent pK(B) values for 3 - 10 nM SR59230A being 8.6 and those for 30 nM - 1 microM being 7.7. 5. These data suggest that beta(3)-adrenoceptors are the predominant beta-adrenoceptor subtype present in the pig bladder and that beta-adrenoceptor mediated responses of this tissue are mediated via both the beta(2)- and beta(3)-adrenoceptor subtypes.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Albuterol / pharmacology
  • Animals
  • Binding, Competitive
  • Dose-Response Relationship, Drug
  • Female
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology*
  • Muscle, Smooth / physiology*
  • Norepinephrine / pharmacology
  • Radioligand Assay
  • Receptors, Adrenergic, beta-3 / drug effects
  • Receptors, Adrenergic, beta-3 / physiology*
  • Swine
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism
  • Urinary Bladder / physiology*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta-3
  • Isoproterenol
  • Albuterol
  • Norepinephrine