Effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and N-omega(6)-nitro-L-arginine methyl ester (NAME) on cyclic GMP levels during muscarinic activation of tracheal smooth muscle

The effects of carbachol on the cyclic GMP (cGMP) content of bovine trachea l smooth muscle in the absence of phosphodiesterase inhibitors were evaluat ed. Carbachol (1 x 10(-5) M) induced two cGMP peaks, at 20 and 60 sec. Both cGMP signals were carbachol concentration-dependent (1 x 10(-11) to 1 x 10 (-5) M), the first being higher than the second. The cGMP signal induction was studied using an inhibitor of the soluble guanylyl cyclase (GC), 1H-[1, 2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), and a nitric oxide (NO) sy nthase inhibitor, N-omega(6)-nitro-L-arginine methyl ester (NAME). ODQ(1 x 10(-7) M) did not affect the second cGMP peak but abolished the first peak, suggesting that a soluble GC may be involved. NAME (1 x 10(-4) M) did not affect the cGMP signals, but changed their 2:1 ratio and also induced a tim e-shift of the first peak to 10 sec and the second to 50 sec. These results indicate that the NO-soluble GC cascade is not responsible for these musca rinic effects on cGMP levels. (C) 1999 Elsevier Science Inc.