RT Journal Article
SR Electronic
T1 Role of Soluble Guanylyl Cyclase in the Relaxations to a Nitric Oxide Donor and to Nonadrenergic Nerve Stimulation in Guinea Pig Trachea and Human Bronchus
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1215
OP 1218
VO 280
IS 3
A1 James L. Ellis
YR 1997
UL http://jpet.aspetjournals.org/content/280/3/1215.abstract
AB The effect of the novel, selective, soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolol[4,3-a]quinoxalin-1-one (ODQ) on the nitric oxide component of the nonadrenergic, noncholinergic relaxation in guinea pig trachea was examined. Relaxant responses to field stimulation (1-16 Hz, 8 V, 1 ms for 15 s) in the presence of indomethacin (3 μM), atropine (1 μM), propranolol (1 μM), α-chymotrypsin (2 U/ml) and histamine (3 μM) were partially inhibited by 0.1 μM ODQ and almost abolished by 1 μM ODQ. In addition, relaxations to the nitric oxide donor 3-morpholinosyndnonimine-N-ethylcarbamide were partially inhibited by 0.1 μM ODQ and abolished by 1 μM ODQ. Relaxations to 3-morpholinosyndnonimine-N-ethylcarbamide in human bronchus were also substantially inhibited by ODQ (1–10 μM). By contrast, relaxations elicited by the stable 3′,5′-cyclic monophosphate analog 8-bromoguanosine-3′,5′-cyclic monophosphate and by isoproterenol were unaffected by 1 μM ODQ in guinea pig trachea and by 10 μM ODQ in human bronchus. These results suggest that relaxant responses to endogenously released or exogenously added nitric oxide in guinea pig trachea and human bronchus are mediated via the activation of soluble guanylyl cyclase and the formation of guanosine-3′,5′-cyclic monophosphate. The American Society for Pharmacology and Experimental Therapeutics