Potassium-evoked efflux of transmitter amino acids and purines from rat cerebral cortex

Abstract

Repeated applications of elevated K + (50 or 75 mM) in cerebral cortical cup superfusates was used to evoke an efflux of γ-aminobutyric acid (GABA), glutamate, aspartate, glycine, adenosine, and inosine from the in vivo rat cerebral cortex. K + (50 mM) significantly elevated GABA levels in cup superfusates but had little effect on the efflux of glutamate, aspartate, glycine, adenosine, or inosine. K + (75 mM) significantly enhanced the efflux of GABA, aspartate, adenosine, and inosine and caused nonsignificant increases in glutamate and glycine efflux. The adenosine A 1 receptor agonist N 6-cyclopentyladenosine (CPA), applied in cup superfusates at a concentration of 10 −10 M had no effect on either basal or K +-evoked release of any of the amino acids or purines measured. At 10 −6 M CPA significantly enhanced aspartate release, and depressed GABA efflux. The selective A 2 adenosine receptor agonist 2-p(2-carboxyethyl) phenethylamino-5′-N-ethyl-carboxamidoadenosine (CGS 21680) (10 −8 M) was without effect on either basal, or K +-evoked, efflux of amino acids or purines. The enhancement of aspartate (an excitotoxic amino acid) efflux by higher concentrations of CPA is likely due to activation of adenosine A 2b receptors. This observation may be of relevance when selecting adenosinergic agents to treat ischemic or traumatic brain injuries. Overall, the results suggest that effects of adenosine receptor agonists on K +-evoked efflux of transmitter amino acids from the in vivo rat cerebral cortex may not be comparable to those observed with in vitro preparations.