Reversal of the desensitized state of pig ovarian follicular human choriogonadotropin-sensitive adenylylcyclase by guanosine 5'-O-(2- thiodiphosphate)

Richard C. Ekstrom, Ellen M. Carney, Marilyn L G Lamm, Mary Hunzicker-Dunn*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

We investigated the stability of the desensitized state of the human choriogonadotropin (hCG)-sensitive adenylylcyclase of the pig ovarian follicle. A 20,000 x g membrane preparation of pig follicular membranes was incubated under conditions which resulted in the hormone-induced desensitization of the hCG-responsive adenylylcyclase. The desensitized state was maintained upon subsequent incubation of the membranes with GTP, GDP, GMP, ATP, ADP, AMP, CTP, UTP, adenyl-5'-yl imidodiphosphate (AMP-P(NH)P), and adenyl (β,γ-methylene)-diphosphonate (AMP-P(CH2)P); however, the desensitized state was reverted to a fully active state upon incubation with guanosine 5'-O-(2-thiodiphosphate) (GDPβS) and guanosine 5'-O-(3- thiotriphosphate) (GTPγS). The reversal effect of GDPβS on hCG-responsive adenylylcyclase activity was time- and temperature-dependent, and showed a selectivity for GDPβS over adenosine 5'-O-(2-thiodiphosphate) (ADPβS) (half-maximal effective dose of 12 μM versus 260 μM, respectively). GDPβS had no effect on the binding affinity or apparent number of luteinizing hormone (LH)/CG receptors or on the dissociation rate of 125I-hCG from the receptor. GDPβS promoted an hCG- and time-dependent release of guanine nucleotides from the membranes. A model is proposed which accounts for the unique characteristics of LH/CG-sensitive adenylylcyclase desensitization and subsequent reactivation by GDPβS.

Original languageEnglish (US)
Pages (from-to)22183-22189
Number of pages7
JournalJournal of Biological Chemistry
Volume267
Issue number31
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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