Inhibitory and Stimulatory Effects of Guanyl-5'-yl Imidodiphosphate on the Adenylate Cyclase Activity of Rat Synaptosomal Fractions1

Abstract

Guanyl-5'-yl imidodiphosphate (Gpp(NH)p), a nucleotide phosphohydrolase-resistant analog of GTP, caused inhibitory and stimulatory effects on the basal adenylate cyclase activity of rat synaptosomal fractions when manganese was present in the assay mixture, whereas the nucleotide caused only a stimulatory effect when magnesium was employed. In the presence of manganese, the inhibitory and stimulatory effects of Gpp(NH)p could be seen at around concentrations of 10(-7) M and 10(-4) M Gpp(NH)p, respectively. The inhibitory and stimulatory effects of Gpp(NH)p were both antagonized competitively by GTP; these effects of the analog were the opposite of those observed with GTP, which was stimulatory and inhibitory for fat call adenylate cyclase at 10(-7) M and 10(-4) M, respectively (Yamamura, H., Lad, P.M., and Rodbell, M. (1977) J. Biol. Chem. 252, 7964--7966). The degree of inhibition by Gpp(NH)p did not depend on the concentration of manganese nor on the addition of ethylene glycol bis(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid.