Analogs of cyclic AMP decreases γ-aminobutyric acid(A) receptor-mediated chloride current in cultured rat hippocampal neurons via an extracellular site

Nevin A Lambert, N. L. Harrison

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22 Citations (Scopus)

Abstract

We have studied the effects of the membrane-permeant cyclic AMP analogs 8-bromo-cyclic AMP and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) on the γ-aminobutyric acid(A) (GABA(A)) receptor-mediated chloride current in cultured rat hippocampal neurons. External perfusion with 8-bromo-cyclic AMP or CPT-cAMP caused a reversible, concentration-dependent decrease in the response to GABA. Adding the protein kinase inhibitor H-8 to the perfusing medium or the intracellular recording solution did not affect the response to GABA, which was decreased by CPT-cAMP as before. L858051, a water-soluble derivative of the adenylate cyclase activator forskolin, did not decrease the response to GABA even in the presence of the phosphodiesterase inhibitor 3-isobutylmethylxanthine. External cyclic AMP also caused a reversible, concentration-dependent decrease in the response to GABA with a potency similar to that of 8-Br-cAMP. When cAMP was present in the intracellular recording solution cAMP and CPT-cAMP decreased the response to GABA as before. These experiments suggest that analogs of cAMP decrease GABA(A) receptor-activated chloride current by acting at an extracellular site.

Original languageEnglish (US)
Pages (from-to)90-94
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume255
Issue number1
StatePublished - Jan 1 1990

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Aminobutyrates
Cyclic AMP
Chlorides
gamma-Aminobutyric Acid
Neurons
8-Bromo Cyclic Adenosine Monophosphate
GABA-A Receptors
L 858051
Phosphodiesterase 3 Inhibitors
Colforsin
Adenylyl Cyclases
Perfusion
Membranes
Water

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

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abstract = "We have studied the effects of the membrane-permeant cyclic AMP analogs 8-bromo-cyclic AMP and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) on the γ-aminobutyric acid(A) (GABA(A)) receptor-mediated chloride current in cultured rat hippocampal neurons. External perfusion with 8-bromo-cyclic AMP or CPT-cAMP caused a reversible, concentration-dependent decrease in the response to GABA. Adding the protein kinase inhibitor H-8 to the perfusing medium or the intracellular recording solution did not affect the response to GABA, which was decreased by CPT-cAMP as before. L858051, a water-soluble derivative of the adenylate cyclase activator forskolin, did not decrease the response to GABA even in the presence of the phosphodiesterase inhibitor 3-isobutylmethylxanthine. External cyclic AMP also caused a reversible, concentration-dependent decrease in the response to GABA with a potency similar to that of 8-Br-cAMP. When cAMP was present in the intracellular recording solution cAMP and CPT-cAMP decreased the response to GABA as before. These experiments suggest that analogs of cAMP decrease GABA(A) receptor-activated chloride current by acting at an extracellular site.",
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