Effects of diadenosine polyphosphates on sodium nitroprusside-induced soluble guanylate cyclase activity in rat cerebellum

Diadenosine polyphosphates (Ap_nAs, n = 1-6 phosphates) have been shown to interact with heme containing proteins and in the present study we determined for guanylate cyclase (GC), a heme containing enzyme whose activity is modulated by adenine nucleotides and nitric oxide, the degree to which Ap_nAs affect sodium nitroprusside (SNP, a nitric oxide donor)-induced GC activity using cytosolic fractions of rat cerebellum and radioimmunoassays for cGMP. SNP-stimulated GC activity was inhibited by up to 60% by Ap_nAs; rank order of potency was Ap₆A > Ap₅A > Ap₄A > Ap₃A = Ap₂A. At concentrations ranging from 0.01 to 100 μM, only Ap₆A potentiated in a concentration-dependent manner (apparent EC₅₀ value 1 μM), by up to two-fold, SNP-induced GC activity. The effects of Ap₆A on GC activity were neither due to changes in SNP degradation nor due to metabolites of Ap₆A. These results suggest that Ap_nAs through its effects on GC activity may play a role in regulating a variety of CNS functions.