A similar pool of cyclic AMP phosphodiesterase in Xenopus oocytes is stimulated by insulin, insulin-like growth factor 1, and [Val12,Thr59]Ha-ras protein.
Pharmacological analysis of in vivo cAMP phosphodiesterase in Xenopus oocytes using the nonselective enzyme inhibitors 3-isobutyl-1-methylxanthine (IBMX), theophylline, and papaverine, demonstrated inhibition of insulin- and insulin-like growth factor-1-induced maturation at concentrations that were 17-60-fold lower than those required to inhibit progesterone-induced germinal vesicle breakdown. The abilities of the phosphodiesterase inhibitors to block the maturation response showed the same rank order of potencies for each hormone: papaverine greater than IBMX greater than theophylline. Insulin-induced oocyte maturation that was accelerated by 0.01 microM progesterone was also inhibited by low micromolar concentrations of IBMX, demonstrating that the accelerated time course was due to a synergistic potentiation of insulin action by progesterone. Both insulin-induced maturation and insulin-stimulated phosphodiesterase activity displayed similar sensitivities to inhibition by IBMX, suggesting that hormone-stimulated phosphodiesterase activity is required for the peptide hormone action. Furthermore, microinjection of the transforming ras gene product [Val12,Thr59]Ha induced oocyte maturation and stimulated oocyte phosphodiesterase activity by approximately 50%, and both of these actions were inhibited by IBMX. These results suggest that oocyte maturation induced by insulin, insulin-like growth factor 1, and transforming ras protein involves stimulation of a similar phosphodiesterase.
Sadler
S E
SE
Department of Pharmacology, University of Colorado School of Medicine, Denver 80262.
Maller
J L
JL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008565:Membrane Proteins / Q000494:pharmacology*; D008845:Microinjections; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010208:Papaverine / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras); D013002:Somatomedins / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology; D013912:Threonine; D014633:Valine; D014981:Xenopus
D007328:Insulin; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D013002:Somatomedins; D013912:Threonine; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D013806:Theophylline; D010208:Papaverine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D016283:Proto-Oncogene Proteins p21(ras); D014633:Valine; D015056:1-Methyl-3-isobutylxanthine