Superoxide dismutase requires ascorbate for activation of cerebral soluble guanylate cyclase

Guanylate cyclase in 100,000 × g supernatant fraction prepared from the rat brain was markedly activated by superoxide dismutase. Although guanylate cyclase in pH 5.0 precipitated fraction prepared from the supernatant fraction failed to be stimulated by superoxide dismutase, the addition of ascorbate restored the responsiveness. Guanylate cyclase in the supernatant fraction which was preincubated with ascorbate oxidase also showed no response to superoxide dismutase. The superoxide dismutase-induced activation of guanylate cyclase in the supernatant fraction as well as in the ascorbate-added pH 5.0 precipitated fraction was completely eliminated by the addition of KCN, diethyldithiocarbamate, Tiron, retinol or hemoglobin.