Skip to main content
Journal cover image

cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.

Publication ,  Journal Article
Heuschneider, G; Schwartz, RD
Published in: Proc Natl Acad Sci U S A
April 1989

The effects of the cyclic nucleotide cAMP on gamma-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner (IC50 = 1.3 mM). The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the gamma-aminobutyric acid-gated Cl- channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36Cl- uptake and generated cAMP with similar potencies (IC50 = 14.3 microM; EC50 = 6.2 microM, respectively). Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl- channel directly. Indeed, forskolin inhibition of muscimol-induced 36Cl- uptake was extremely rapid (within 5 sec), preceding the accumulation of sufficient levels of cAMP. After 5 min, a slower phase of inhibition was seen, similar to the time course for cAMP accumulation. The data suggest that gamma-aminobutyric acid (GABAA) receptor function in brain can be regulated by cAMP-dependent phosphorylation.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 1989

Volume

86

Issue

8

Start / End Page

2938 / 2942

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synaptosomes
  • Rats
  • Muscimol
  • Membrane Proteins
  • In Vitro Techniques
  • Cyclic AMP
  • Colforsin
  • Chlorides
  • Chloride Channels
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Heuschneider, G., & Schwartz, R. D. (1989). cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A, 86(8), 2938–2942. https://doi.org/10.1073/pnas.86.8.2938
Heuschneider, G., and R. D. Schwartz. “cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.Proc Natl Acad Sci U S A 86, no. 8 (April 1989): 2938–42. https://doi.org/10.1073/pnas.86.8.2938.
Heuschneider G, Schwartz RD. cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2938–42.
Heuschneider, G., and R. D. Schwartz. “cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.Proc Natl Acad Sci U S A, vol. 86, no. 8, Apr. 1989, pp. 2938–42. Pubmed, doi:10.1073/pnas.86.8.2938.
Heuschneider G, Schwartz RD. cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2938–2942.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 1989

Volume

86

Issue

8

Start / End Page

2938 / 2942

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synaptosomes
  • Rats
  • Muscimol
  • Membrane Proteins
  • In Vitro Techniques
  • Cyclic AMP
  • Colforsin
  • Chlorides
  • Chloride Channels