Amphibian oocyte maturation and protein synthesis: Related inhibition by cyclic AMP, theophylline, and papaverine

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Abstract
Two inhibitors of cyclic[c]AMP phosphodiesterase (3'':5''-cyclic-AMP 5''-nucleotidohydrolase, EC 3.1.4.17), theophylline and papaverine, inhibited the maturation of Xenopus laevis oocytes induced by 4 different stimuli: human chorionic gonadotropin hCG, progesterone, testosterone and La. Addition of I mM cAMP to the medium delays maturation by approximately 2 h. Papaverine, theophylline and cAMP inhibit amino acid incorporation into oocyte proteins by 50% or more but do not inhibit amino acid uptake. The capacity of theophylline to block maturation and protein synthesis is reversed in a parallel fashion by addition of 1-5 mM Ca2+ to the medium. Addition of papaverine, theophylline and cycloheximide to oocytes at different times after hormonal treatment shows that the step sensitive to blockage by the 3 drugs is coincident and precedes germinal vesicle breakdown by about 1.5 h. Theophylline and papaverine did not increase endogenous cAMP levels in oocytes but blocked the decrease of cAMP levels observed 3 h after progesterone treatment. Both drugs inhibit oocyte cAMP phosphodiesterase measured in vivo and severely inhibit the stimulus of Ca uptake caused by progesterone and hCG. CAMP, theophylline and papaverine may block oocyte maturation by inhibiting protein synthesis, possibly via a cAMP-dependent protein kinase.