title: Type III phosphodiesterase plays a necessary role in the growth-promoting actions of insulin, insulin-like growth factor-I, and Ha p21ras in Xenopus laevis oocytes.
abstract: Three phosphodiesterase (PDE) type III inhibitors were tested and found to inhibit Xenopus oocyte maturation induced by insulin with apparent IC50 values of 2.2 +/- 0.2 microM Cl-930, 25 +/- 3 microM imazodan (Cl-914), and 786 +/- 237 microM piroximone (MDL 19,205). The same rank order of potencies was observed for inhibition of insulin-like growth factor-I (IGF-I)-induced oocyte maturation, with IC50 values of 5.5 +/- 0.9 microM Cl-930, 54 +/- 4 microM imazodan, and 1190 +/- 395 microM piroximone. Oocyte maturation induced by microinjection of Ha p21ras was also inhibited by pretreatment of oocytes with Cl-930 or imazodan, with IC50 values of 4.3 +/- 1.2 and 59 +/- 4 microM, respectively. Progesterone-induced maturation was not affected by PDE III inhibitor action; and, neither type IV PDE inhibitors (Ro 20, 1724 or rolipram) nor dipyridamole (a type V PDE inhibitor) inhibited cell division induced by IGF-I or microinjected Ha p21ras. In addition, while insulin-stimulated oocyte PDE activity measured in vivo after microinjection of 200 microM [3H] cAMP was inhibited by nonselective and type III-specific drugs (with IC50 values of 4.2 +/- 1.8 microM Cl-930 and 26 +/- 6 microM imazodan), type IV and type V inhibitors did not inhibit hormone-stimulated enzyme activity. This pharmacological evidence demonstrates a necessary role for PDE III in insulin-, IGF-I-, and p21ras-induced meiotic cell division in Xenopus laevis oocytes.
authors.affiliation: Department of Biological Sciences, University of Denver, Colorado 80208.
authors.forename: S E
authors.initials: SE
authors.lastname: Sadler
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D006128:Growth / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D008540:Meiosis / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D015689:Oncogene Protein p21(ras) / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009866:Oogenesis / Q000187:drug effects / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D007328:Insulin; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015689:Oncogene Protein p21(ras)