Molecular Endocrinology, Vol 5, 1939-1946, Copyright © 1991 by Endocrine Society

ARTICLES

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

SE Sadler
Department of Biological Sciences, University of Denver, Colorado 80208.

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.

This article has been cited by other articles:

				W. Zhang and R. W. Colman Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A Blood, September 1, 2007; 110(5): 1475 - 1482. [Abstract] [Full Text] [PDF]

				S. E. Sadler and N. D. Jacobs Stimulation of Xenopus laevis Oocyte Maturation by Methyl-{beta}-Cyclodextrin Biol Reprod, June 1, 2004; 70(6): 1685 - 1692. [Abstract] [Full Text] [PDF]

				F. J. Richard, A. Tsafriri, and M. Conti Role of Phosphodiesterase Type 3A in Rat Oocyte Maturation Biol Reprod, November 1, 2001; 65(5): 1444 - 1451. [Abstract] [Full Text] [PDF]

				M. Conti Phosphodiesterases and Cyclic Nucleotide Signaling in Endocrine Cells Mol. Endocrinol., September 1, 2000; 14(9): 1317 - 1327. [Full Text]

				E. R. Hernandez Embryo implantation and GnRH antagonists: Embryo implantation: the Rubicon for GnRH antagonists Hum. Reprod., June 1, 2000; 15(6): 1211 - 1216. [Abstract] [Full Text] [PDF]

				F. Ahmad, L.-N. Cong, L. Stenson Holst, L.-M. Wang, T. Rahn Landstrom, J. H. Pierce, M. J. Quon, E. Degerman, and V. C. Manganiello Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells J. Immunol., May 1, 2000; 164(9): 4678 - 4688. [Abstract] [Full Text] [PDF]

				C. B. Andersen, R. A. Roth, and M. Conti Protein Kinase B/Akt Induces Resumption of Meiosis in Xenopus Oocytes J. Biol. Chem., July 24, 1998; 273(30): 18705 - 18708. [Abstract] [Full Text] [PDF]

				C. L. Chik, B. Li, E. Karpinski, and A. K. Ho Insulin and Insulin-Like Growth Factor-I Inhibit the L-Type Calcium Channel Current in Rat Pinealocytes Endocrinology, May 1, 1997; 138(5): 2033 - 2042. [Abstract] [Full Text] [PDF]

				E. Degerman, P. Belfrage, and V. C. Manganiello Structure, Localization, and Regulation of cGMP-inhibited Phosphodiesterase (PDE3) J. Biol. Chem., March 14, 1997; 272(11): 6823 - 6826. [Full Text] [PDF]