Single GABAergic synaptic terminals from rat midbrain exhibit functional P2X and dinucleotide receptors, able to induce GABA secretion

GABAergic terminals from rat midbrain characterized by immunolocalization o f glutamic acid decarboxylase and/or the vesicular inhibitory amino acid tr ansporter respond to ATP or P-1, P-5-di(adenosine-5 ') pentaphosphate (Ap(5 )A) with an increase in the intrasynaptosomal calcium concentration measure d by a microfluorimetric technique in single synaptic terminals. The ATP re sponse is mediated through the activation of P2X receptors with an abundant presence of P2X(3) subunits. Ap(5)A, however, exerts its effects by acting through a different receptor termed the dinucleotide receptor. Both recept ors, once activated in the presence of extrasynaptosomal calcium, induce a concentration-dependent GABA release from synaptosomal populations with EC5 0 values of 16 and 20 muM for ATP and Ap(5)A, respectively. Specific inhibi tion of GABA release is obtained with pyridoxal phosphate-6-azophenyl-2 ' , 4 ' -disulphonic acid (80 muM) on the ATP effect and with P-1, P-5-di(inosi ne-5 ') pentaphosphate (100 nM) on the dinucleotide receptor.