Stimulation of muscarinic M2 receptors inhibits atrial natriuretic peptide-mediated relaxation in bovine tracheal smooth muscle

The influence of muscarinic M(2) receptors to modulate the relaxant effects of atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) was investigated in bovine tracheal smooth muscle. In bovine tracheal smooth muscles contracted with methacholine (0.3 micro M), methoctramine (0.03 micro M), a selective muscarinic M(2) receptor antagonist, augmented the relaxant responses to ANP without affecting the responses to SNP and 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate. Pertussis toxin (PTX; 200 ng/ml for 18 h) augmented the relaxation and accumulation of guanosine 3',5'-cyclic monophosphate produced by ANP. These results suggest that the stimulation of muscarinic M(2) receptors suppresses ANP-induced activation of particulate guanylyl cyclase via a PTX-sensitive G protein.