Muscarinic receptor subtypes and signalling involved in the attenuation of isoprenaline-induced rat urinary bladder relaxation
| Autor: | Noach de Haas, Eric L. Stangeland, Tod Steinfeld, Mathai Mammen, Lambertus P. W. Witte, Martin C. Michel, Jayashree Aiyar |
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| Přispěvatelé: | Urology, Other Research, Pharmacology and pharmacotherapeutics |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Relaxation medicine.medical_specialty Carbachol Muscle Relaxation Urinary Bladder M2 muscarinic receptor Stimulation Muscarinic Antagonists Muscarinic Agonists Muscarinic agonist THRX-182087 03 medical and health sciences 0302 clinical medicine Internal medicine Isoprenaline Receptors Adrenergic beta Muscarinic acetylcholine receptor medicine Animals Rats Wistar Receptor β-Adrenoceptor M3 muscarinic receptor 030304 developmental biology Receptor Muscarinic M3 Pharmacology Receptor Muscarinic M2 0303 health sciences Chemistry Isoproterenol Muscarinic acetylcholine receptor M3 General Medicine Adrenergic beta-Agonists Rats Muscle relaxation Endocrinology Original Article 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology; Vol 384 Naunyn-Schmiedeberg's Archives of Pharmacology Naunyn-Schmiedeberg s archives of pharmacology, 384(6), 555-563. Springer Verlag |
| ISSN: | 0028-1298 |
| DOI: | 10.1007/s00210-011-0689-8 |
| Popis: | 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 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 β-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. |
| Databáze: | OpenAIRE |
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