Muscarinic receptor subtypes and signalling involved in the attenuation of isoprenaline-induced rat urinary bladder relaxationReport as inadecuate




Muscarinic receptor subtypes and signalling involved in the attenuation of isoprenaline-induced rat urinary bladder relaxation - Download this document for free, or read online. Document in PDF available to download.

Naunyn-Schmiedeberg-s Archives of Pharmacology

, Volume 384, Issue 6, pp 555–563

First Online: 24 September 2011Received: 25 April 2011Accepted: 26 August 2011

Abstract

β-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 β-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 M3-sparing muscarinic agonist, providing selective M2 stimulation in rat bladder, and THRX-182087 as a highly M2-selective antagonist. The use of BZI and of THRX-182087 in the presence of carbachol enabled experimental conditions with a selective stimulation of only M2 or M3 receptors, respectively. Confirming previous findings, carbachol attenuated isoprenaline-induced detrusor relaxation. M2-selective stimulation partly mimicked this attenuation, indicating that both M2 and M3 receptors are involved. During M3-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 M2 and M3 receptors contribute to attenuation of β-adrenoceptor-mediated relaxation of rat urinary bladder; the signal transduction pathway involved in the M3 component of this attenuation differs from that mediating direct contractile effects of M3 receptors.

KeywordsM2 muscarinic receptor M3 muscarinic receptor THRX-182087 β-Adrenoceptor Relaxation Urinary bladder  Download fulltext PDF



Author: Lambertus P. W. Witte - Noach de Haas - Mathai Mammen - Eric L. Stangeland - Tod Steinfeld - Jayashree Aiyar - Martin C

Source: https://link.springer.com/







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