Potassium-evoked efflux of transmitter amino acids and purines from rat cerebral cortex.
Repeated applications of elevated K+ (50 or 75 mM) in cerebral cortical cup superfusates was used to evoke an efflux of gamma-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 A1 receptor agonist N6-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 A2 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 A2b 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.
Phillis
J W
JW
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201.
Perkins
L M
LM
O'Regan
M H
MH
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011687:Purines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D000959:Antihypertensive Agents; D018377:Neurotransmitter Agents; D010627:Phenethylamines; D011687:Purines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; D011188:Potassium