科研之友
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摘要
beta-Adrenoceptors are important mediators of smooth muscle relaxation in the urinary bladder, but the concomitant presence of a muscarinic agonist, e.g., carbachol, can attenuate relaxation responses by reducing potency and/or efficacy of beta-adrenoceptor agonists such as isoprenaline. Therefore, the present study was designed to explore the subtypes and signalling pathways of muscarinic receptors involved in the attenuation of isoprenaline-induced isolated rat detrusor preparations using novel subtype-selective receptor ligands. In radioligand binding studies, we characterized BZI to be a M-3-sparing muscarinic agonist, providing selective M-2 stimulation in rat bladder, and THRX-182087 as a highly M-2-selective antagonist. The use of BZI and of THRX-182087 in the presence of carbachol enabled experimental conditions with a selective stimulation of only M-2 or M-3 receptors, respectively. Confirming previous findings, carbachol attenuated isoprenaline-induced detrusor relaxation. M-2-selective stimulation partly mimicked this attenuation, indicating that both M-2 and M-3 receptors are involved. During M-3-selective stimulation, the attenuation of isoprenaline responses was reduced by the phospholipase C inhibitor U 73,122 but not by the protein kinase C inhibitor chelerythrine. We conclude that both M-2 and M-3 receptors contribute to attenuation of beta-adrenoceptor-mediated relaxation of rat urinary bladder; the signal transduction pathway involved in the M-3 component of this attenuation differs from that mediating direct contractile effects of M-3 receptors.
- 出版日期2011-12
