TY - JOUR T1 - Analogs of cyclic AMP decrease gamma-aminobutyric acidA receptor-mediated chloride current in cultured rat hippocampal neurons via an extracellular site. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 90 LP - 94 VL - 255 IS - 1 AU - N A Lambert AU - N L Harrison Y1 - 1990/10/01 UR - http://jpet.aspetjournals.org/content/255/1/90.abstract N2 - 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. ER -