Adenosine inhibits glutamate exocytosis largely without interfering with Ca2+ influx in rat cerebrocortical synaptosomes.
Adenosine is an inhibitor of glutamate release in synaptosomes. The inhibition is removed by the A(1) adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). We monitored the variations of cytoplasmic free Ca(2+) concentrations ([Ca(2+)](i)) in KCl or 4-aminopyridine-stimulated synaptosomes, in the presence of adenosine or adenosine plus DPCPX. The increment of [Ca(2+)](i) upon stimulation was unmodified by adenosine (up to 400-500 microM) while it was strongly decreased when exocytosis was decreased to a similar extent by lowering KCl or 4-aminopyridine. Adenosine also inhibited glutamate release induced by the Ca(2+) ionophore ionomycin. Increasing adenosine to 1.5 mM resulted in a decrease of the stimulus-induced increase of [Ca(2+)](i) and in the further potentiation of the adenosine inhibition of exocytosis from 41+/-3 to 51+/-4%. We conclude that adenosine affects glutamate exocytosis mostly in a Ca(2+) independent mode.
Zoccarato
F
F
Department of Biological Chemistry and C.N.R. Unit for the study of Biomembranes, University of Padova, Viale G. Colombo, 3, 35121 Padova, Italy. zoccarat@civ.bio.unipd.it
Cavallini
L
L
Alexandre
A
A
D000241:Adenosine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000700:Analgesics; D018698:Glutamic Acid; D000241:Adenosine; D002118:Calcium