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.
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.
Cátedra de Patología General y Fisiopatología, Instituto de Medicina Experimental, Universidad Central de Venezuela, Caracas.
L
L
Guerra de González
A
A
Misle
G
G
Pacheco
V
V
Napoleón de Herrera
R
R
González de Alfonzo
I
I
Lippo de Bécemberg
M J
MJ
Alfonzo
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014132:Trachea
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D010069:Oxadiazoles; D011810:Quinoxalines; D011976:Receptors, Muscarinic; D002217:Carbachol; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester