Analogs of cyclic AMP decrease gamma-aminobutyric acidA receptor- mediated chloride current in cultured rat hippocampal neurons via an extracellular site

NA Lambert and NL Harrison

Laboratory of Neurophysiology, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.

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 gamma-aminobutyric acidA (GABAA) 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 GABAA receptor- activated chloride current by acting at an extracellular site.

Volume 255, Issue 1, pp. 90-94, 10/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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