NITRIC-OXIDE (NO-CENTER-DOT), THE ONLY NITROGEN MONOXIDE REDOX FORM CAPABLE OF ACTIVATING SOLUBLE GUANYLYL CYCLASE

In the present study, we determined that of the redox forms of nitroge n monoxide, NO-, NO . and NO+, only NO . significantly- activates solu ble 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 r elative to the basal activity level. Interference by other reaction pr oducts was eliminated as a possible explanation for the lack of activa tion. To the extent that NO+ could be stabilized in aqueous solution, by dissolution of the nitrosonium salt NOPF6 in dry organic solvent Dr ier to addition to the enzyme in buffer, NO+ had no effect on the acti vity 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 i dentical with endothelium-derived relaxing factor, the physiological r egulator of soluble guanylyl cyclase activity.