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

• Published in: Biochemical pharmacology 1999-08, Vol.58 (4), p.563-569
• Main Authors: Guerra de González, L, Misle, A, Pacheco, G, Napoleón de Herrera, V, González de Alfonzo, R, Lippo de Bécemberg, I, Alfonzo, M J
• Format: Article
• Language: English
• Subjects: Animals; Carbachol - pharmacology; Cattle; Cyclic GMP - metabolism; Enzyme Inhibitors - pharmacology; Guanylate Cyclase - antagonists & inhibitors; In Vitro Techniques; Muscarinic Agonists - pharmacology; Muscle, Smooth - drug effects; Muscle, Smooth - enzymology; Muscle, Smooth - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Oxadiazoles - pharmacology; Quinoxalines - pharmacology; Receptors, Muscarinic - metabolism; Trachea
• ISSN: 0006-2952

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-a]quinoxalin-1-one (ODQ), and a nitric oxide (NO) synthase inhibitor, Nomega(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.