ADENOSINE-A1 RECEPTOR-MEDIATED INHIBITION OF EVOKED GLUTAMATE RELEASEIS COUPLED TO CALCIUM INFLUX DECREASE IN GOLDFISH BRAIN SYNAPTOSOMES

Binding of [H-3]cyclohexyladenosine (CHA) to the cellular fractions an d P2 subfractions of the goldfish brain was studied. The A1 receptor d ensity was predominantly in synaptosomal membranes. In goldfish brain synaptosomes (P2), 30 mM K+ stimulated glutamate, taurine and GABA rel ease in a Ca2+-dependent fashion, whereas the aspartate release was Ca 2+-independent. Adenosine, R-phenylisopropyladenosine (R-PIA) and CHA (100 muM) inhibited K+-stimulated glutamate release (31%, 34% and 45%, respectively). All of these effects were reversed by the selective ad enosine A1 receptor antagonist, 8-cyclopentyltheophylline (CPT). In th e same synaptosomal preparation, K+ (30 mM) stimulated Ca2+ influx (46 .8 +/- 6.8%) and this increase was completely abolished by pretreatmen t with 100 nM omega-conotoxin. Pretreatment with 100 muM R-PIA or 100 muM CHA, reduced the evoked increase of intra-synaptosomal Ca2+ concen tration, respectively by 37.7 +/- 4.3%, and 39.7 +/- 9.0%. A possible correlation between presynaptic A1 receptor inhibition of glutamate re lease and inhibition of calcium influx is discussed.