CYTIDYLATE CYCLASE ACTIVITY IS STIMULATED VIA ACTIVATION OF A GUANINE NUCLEOTIDE-BINDING PROTEIN

Cytidylate cyclase is a membrane-bound enzyme which catalyzes the biosynthesis of cytidine 3',5'-cyclic monophosphate (cCMP) from CTP. By using a sensitive and specific enzyme immunoassay method, we evaluated the participation of guanine nucleotide-binding protein (G-protein) in the regulation of cytidylate cyclase activity in rat brain and other tissues. AlF4-, an activator of G-proteins, effectively elevated the cyclase activity. The stimulation by GTPgammaS, a nonhydrolyzable GTP analogue, was also observed in time- and concentration-dependent manner during the preincubation and this effect was competitively inhibited by the addition of GDPbetaS. However, islet-activating protein and cholera toxin which affected adenylate cyclase activity had no effect on cytidylate cyclase activity. These results indicate that cytidylate cyclase is associated with a certain G-protein and its activity is regulated by the mode different from that of adenylate cyclase.