Effects of valproic acid on β-adrenergic receptors, G-proteins, and adenylyl cyclase in rat C6 glioma cells

Guang Chen, Husseini K. Manji, Clinton B. Wright, David B. Hawver, William Z. Potter

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the treatment of mania. In the present study, we found that chronic exposure of rat C6 glioma cells to VPA induces a coordinate decrease in multiple components of the β-adrenergic receptor- (β-AR) coupled cyclic adenosine 3'-5'monophosphate (cAMP) generating system. Chronic VPA decreased the number of β-ARs in a time- and concentration-dependent manner; the decrease of β-ARs was largely β1-AR selective and affected β-ARs in both the high- and low-affinity states. Chronic VPA also significantly attenuated receptor- and postreceptor-stimulated cAMP production, [3H]forskolin binding sites, immunolabeling of Gα(s) 45, and cholera toxin catalyzed ADP-ribosylation of Gα(s) 52 and 45. Although the precise underlying mechanisms remain to be elucidated, such profound long-term changes in the functioning of this key signaling pathway may help explain the antimanic effects of chronic VPA treatment and are worthy of further study.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalNeuropsychopharmacology
Volume15
Issue number3
DOIs
StatePublished - Sep 1996

Keywords

  • β-adrenergic receptor
  • Adenylyl cyclase
  • Anticonvulsant
  • Bipolar affective disorder
  • Guanine-nucleotide-binding protein
  • Lithium
  • Protein kinase C
  • Valproic acid

ASJC Scopus subject areas

  • Pharmacology

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