The effect of nucleotides and adenosine on stimulus-evoked glutamate release from rat brain cortical slices.
Evidence has previously been presented that P1 receptors for adenosine, and P2 receptors for nucleotides such as ATP, regulate stimulus-evoked release of biogenic amines from nerve terminals in the brain. Here we investigated whether adenosine and nucleotides exert presynaptic control over depolarisation-elicited glutamate release. Slices of rat brain cortex were perfused and stimulated with pulses of 46 mM K(+) in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (0.2 mM). High K(+) substantially increased efflux of glutamate from the slices. Basal glutamate release was unchanged by the presence of nucleotides or adenosine at concentrations of 300 microM. Adenosine, ATP, ADP and adenosine 5'-O-(3-thiotriphoshate) at 300 microM attenuated depolarisation-evoked release of glutamate. However UTP, 2-methylthio ATP, 2-methylthio ADP, and alpha,beta-methylene ATP at 300 microM had no effect on stimulated glutamate efflux. Adenosine deaminase blocked the effect of adenosine, but left the response to ATP unchanged. The A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine antagonised the inhibitory effect of both adenosine and ATP. Cibacron blue 3GA inhibited stimulus-evoked glutamate release when applied alone. When cibacron blue 3GA was present with ATP, stimulus-evoked glutamate release was almost eliminated. However, this P2 antagonist had no effect on the inhibition by adenosine. These results show that the release of glutamate from depolarised nerve terminals of the rat cerebral cortex is inhibited by adenosine and ATP. ATP appears to act directly and not through conversion to adenosine.
Bennett
G C
GC
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN.
Boarder
M R
MR
D000241:Adenosine / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology*; D058910:Purinergic P2 Receptor Agonists; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014227:Triazines / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D009711:Nucleotides; D058910:Purinergic P2 Receptor Agonists; D011759:Pyrrolidines; D014227:Triazines; D014970:Xanthines; D018698:Glutamic Acid; C012842:Cibacron Blue F 3GA; C083486:pyrrolidine-2,4-dicarboxylic acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000243:Adenosine Deaminase; D000241:Adenosine