Cyclic AMP‐Dependent Protein Kinase Decreases γ‐Aminobutyric AcidA Receptor‐Mediated 36Q1 Uptake by Brain Microsacs

Nancy J. Leidenheimer, Tina K. Machu, Shuichi Endo, Richard W. Olsen, R. Adron Harris, Michael D. Browning

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The effect of cyclic AMP (cAMP)‐dependent protein phosphorylation on γ‐aminobutyric acidA (GABAA) receptor function was examined using isolated brain membrane vesicles (microsacs). Muscimol‐stimulated 36C1 uptake was studied in mouse brain microsacs permeabilized to introduce the catalytic subunit of cAMP‐ dependent protein kinase (PKA). At both submaximal and maximally effective concentrations of muscimol, PKA inhibited muscimol‐stimulated 36C1 uptake by ∼25%. Jn parallel experiments, PKA and [γ‐32P]ATP were introduced into the microsacs, and we attempted to immunoprecipitatc the entire GABAA receptor complex, under nondenaturing conditions, using an anti‐α1‐subunit antibody. Data from such experiments show that PKA increases the phosphorylation of several microsac proteins, including a 66‐kDa polypeptide specifically immunoprecipitated with the GABAA receptor anti‐α1 subunit antibody. Phosphopeptide mapping of the 66‐kDa polypeptide demonstrated a 14‐kDa fragment similar to that obtained with the purified, PKA‐phosphorylated GABAA receptor. These results provide evidence that the catalytic subunit of PKA inhibits the function of brain G ABAAreceptors and demonstrate that this functional change is concomitant with an increase in protein phosphorylation.

Original languageEnglish
Pages (from-to)722-725
Number of pages4
JournalJournal of Neurochemistry
Volume57
Issue number2
DOIs
StatePublished - Aug 1991

Keywords

  • Brain microsacs
  • C1uptake
  • Cyclic AMP‐dependent protein kinase
  • Muscimol
  • Protein phosphorylation
  • ‐γ‐Aminobutyric acid receptor

Fingerprint Dive into the research topics of 'Cyclic AMP‐Dependent Protein Kinase Decreases γ‐Aminobutyric Acid<sub>A</sub> Receptor‐Mediated <sup>36</sup>Q1<sup>−</sup> Uptake by Brain Microsacs'. Together they form a unique fingerprint.

Cite this