Progesterone inhibition of Xenopus oocyte adenylate cyclase is not mediated via the Bordetella pertussis toxin substrate.

Preincubation of intact Xenopus laevis oocytes with islet-activating protein (IAP) stimulates plasma membrane adenylate cyclase activity measured in the presence of either GTP or 5'-guanylyl imidodiphosphate. The toxin appears to act by catalyzing the ADP-ribosylation of a 41,000-D protein in the oocyte plasma membrane that is distinct from the 45,000- and 52,000-D proteins labeled by cholera toxin. Preincubation of intact oocytes with IAP for 2.5 hr inhibits 80% of the ADP-ribosylation of oocyte membranes subsequently prepared and treated in vitro with IAP in the presence of [alpha-32P]NAD. The abilities of progesterone and the P site agonist, 2',5'-dideoxyadenosine, to inhibit plasma membrane adenylate cyclase are not inhibited by IAP treatment, but IAP pretreatment abolishes inhibition by acetylcholine. In addition, IAP pretreatment of oocytes slows the time course of germinal vesicle breakdown induced by suboptimal concentrations of progesterone. This effect of toxin upon oocyte maturation is apparently due to its effect upon basal cyclase activity, since IAP has no effect upon the time course of maturation induced by 10 microM progesterone. These results indicate that, even though the oocyte adenylate cyclase does contain a functional Ni subunit, inhibition of Xenopus oocyte adenylate cyclase by progesterone or 2',5'-dideoxyadenosine is not mediated via the Bordetella pertussis toxin substrate.