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

ABSTRACT

Diadenosine polyphosphates (ApnAs,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 ApnAs 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 ApnAs; rank order of potency was Ap6A > Ap5A > Ap4A > Ap3A = Ap2A. At concentrations ranging from 0.01 to 100 microM, only Ap6A potentiated in a concentration-dependent manner (apparent EC50 value 1 microM), by up to two-fold, SNP-induced GC activity. The effects of Ap6A on GC activity were neither to changes in SNP degradation nor due to metabolites of Ap6A. These results suggest that ApnAs through its effects on GC activity may play a role in regulating a variety of CNS functions.