Muscarinic agonists acting through M2 acetylcholine receptors stimulate the migration of an NO-sensitive guanylyl cyclase to the plasma membrane of bovine tracheal smooth muscle

作者：Placeres Uray Fabiola; Gonzalez de Alfonzo Ramona; Lippo de Becemberg Itala; Alfonzo Marcelo J^*

来源：Journal of Receptors and Signal Transduction, 2010, 30(1): 10-23.

DOI：10.3109/10799890903325585

• Tracheal smooth muscle
• cGMP
• NO-sensitive sGC
• Muscarinic receptors
• G proteins

Muscarinic agonists acting on bovine tracheal smooth muscle (BTSM) induce two separate cGMP signals, one at 20 sec associated with NO-sensitive-soluble-guanylyl-cyclase (NO-sGC) and another at 60 sec, linked to natriuretic-peptide-GC. The 20-sec-cGMP novel cascade starts with mAChRs, via unknown components, activates an NO-sGC. To unravel this cascade, in crude membranes isolated from intact BTSM strips exposed to muscarinic agonists, we detected GC activities increments at 20 sec and 60 sec. The 20-sec-GC is a NO-sensitive-GC, identified as alpha(1)beta(1)-heterodimer. In reconstitution experiments with purified plasma membranes and cytosol, muscarinic agonists induced an NO-sGC migration in a dose-dependent manner, being inhibited by muscarinic antagonists displaying an M(2)AChR profile and blocked by PTX, suggesting the involvement of G(o)/G(i) proteins. The NO-sGC related to migration was isolated and identified as an alpha(1)beta(1)-heterodimer. This work shows that muscarinic agonists in BTSM induce a massive and selective alpha(1)beta(1)-NO-sGC migration from cytoplasm to plasma membranes being responsible for the 20-sec-cGMP signal.

• 出版日期2010-2