STIMULATION OF SOLUBLE GUANYLATE-CYCLASE BY SUPEROXIDE-DISMUTASE IS MEDIATED BY NO

Soluble guanylate cyclase (sGC), which is found in many cells and tiss ues, represents the receptor for the intra- and intercellular messenge r molecule NO. Superoxide dismutase (SOD), an enzyme involved in the d egradation of toxic superoxide radicals, has been proposed as a non-NO activator of sGC. Here we show that SOD stimulated sGC purified from bovine lung up to 10-fold. Activation by SOD was not influenced by the hydroxyl radical scavengers mannitol and DMSO. In contrast, the prese nce of the NO scavengers oxyhaemoglobin and yl)-4,4,5,5-tetramethylimi dazoline-1-oxyl-3-oxide, as well as the O-2(-)-generating system xanth ine oxidase/hypoxanthine, led to inhibition of SOD-stimulated cGMP pro duction. NO-insensitive sGC mutants were not influenced either by SOD or by xanthine oxidase. We have previously shown that sGC was stimulat ed by NO present in the normal atmosphere. Here;we show that the SOD e ffect depended on the NO concentration from the atmosphere, as the sti mulation of sGC by defined NO gases (0, 120, 330 and 1000 parts per bi llion NO) was potentiated by SOD. NO stimulation of sGC and its potent iation by SOD were inhibited by oxyhaemoglobin to identical levels. We conclude that the SOD-mediated stimulation of sGC is due to the elimi nation of superoxide, thereby preventing its reaction with NO to form peroxynitrite.