Long-term effect of forskolin on the activation of adenylyl cyclase in astrocytes

Amina El Jamali, Nadia Rachdaoui, Claude Jacquemin, Claude Corrèze

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Long-term (48-h) forskolin treatment of rat astroglial cells led to a slight decrease (30-40%) in the response to isoproterenol, vasoactive- intestinal peptide, guanyl 5'-(βγ-imido)diphosphate, guanosine 5'-O-(3- thiotriphosphate) [GTP(S)], and AIF4 in crude membrane fractions. In contrast, the acute stimulatory effect of forskolin was increased by 1.25- 1.5-fold. These two opposite effects of forskolin were mediated by a cyclic AMP-dependent mechanism. No changes in G(s)α, G(i)α, or Gβ protein levels could be determined by immunoblotting using specific antisera. No significant differences were observed in the ability of G proteins extracted from control and forskolin-treated cells to reconstitute a full adenylyl cyclase activity in membranes from S49 cyc cells, lacking G(s)α protein. G(s)α proteins were detected in two pools of membranes, one in the heavy sucrose fractions and the other in light sucrose fractions. Forskolin treatment of the cells shifted G(s)α protein toward the light-density membranes. We did not find any significant change in the distribution of adenylyl cyclase. In contrast to the decreased stimulation of adenylyl cyclase activity by agonists acting via G(s)α, observed in the crude membrane fraction, the responses of adenylyl cyclase to forskolin as well as to GTP(S) were increased in the purified plasma membrane fractions. These results may indicate that sensitization of the catalyst appears to be the dominant component in the astroglial cell response to long-term treatment by forskolin.

Original languageEnglish (US)
Pages (from-to)2532-2539
Number of pages8
JournalJournal of neurochemistry
Volume67
Issue number6
DOIs
StatePublished - Dec 1996

Keywords

  • ATP pyrophosphate-lyase (cyclizing) (EC 4.6.1.1)
  • Astroglial cells
  • Desensitization
  • G protein
  • Subcellular fractionation
  • Up- regulation
  • Western blotting

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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