The role of beta(3)-adrenoceptors in mediating relaxation of porcine detrusor muscle.
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.
Yamanishi
Tomonori
T
Department of Biomedical Science, University of Sheffield, Sheffield. yamanish@dokkyomed.ac.jp
Chapple
Christopher R
CR
Yasuda
Kosaku
K
Yoshida
Kenichiro
K
Chess-Williams
Russell
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011869:Radioligand Assay; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D022702:Receptors, Adrenergic, beta-3; D007545:Isoproterenol; D000420:Albuterol; D009638:Norepinephrine