Nitric oxide (NO), the only nitrogen monoxide redox form capable of activating soluble guanylyl cyclase.
In the present study, we determined that of the redox forms of nitrogen monoxide, NO-, NO and NO+, only NO significantly activates soluble guanylyl cyclase (GTP pyrophosphate-lyase cyclizing, EC 4.6.1.2). Neither of the NO-donors tested, Angeli's salt (Na2N2O3) or Piloty's acid (C6H5SO2NHOH), caused a change in the guanylyl cyclase activity relative to the basal activity level. Interference by other reaction products was eliminated as a possible explanation for the lack of activation. To the extent that NO+ could be stabilized in aqueous solution, by dissolution of the nitrosonium salt NOPF6 in dry organic solvent prior to addition to the enzyme in buffer, NO+ had no effect on the activity of soluble guanylyl cyclase. The counter-ion, PF6-, had a minimal effect on the enzyme activity and, therefore was, not responsible for the lack of activation by NO+. These observations suggest that NO- is the natural activator of soluble guanylyl cyclase and is reasonably identical with endothelium-derived relaxing factor, the physiological regulator of soluble guanylyl cyclase activity.
Dierks
E A
EA
Department of Chemistry, University of Wisconsin, Madison 53706, USA.
Burstyn
J N
JN
D000143:Acids / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D012492:Salts / Q000494:pharmacology
D000143:Acids; D002412:Cations; D012492:Salts; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D010100:Oxygen