Effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and Nω(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 tracheal smooth muscle in the absence of phosphodiesterase inhibitors were evaluated. 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) synthase 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 time-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 muscarinic effects on cGMP levels. (C) 1999 Elsevier Science Inc.