Cytidylate cyclase activity is stimulated via activation of a guanine nucleotide-binding protein

Abstract 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. AlF 4 − , an activator of G-proteins, effectively elevated the cyclase activity. The stimulation by GTPγS, 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 GDPβS. 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.