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 of glutamic acid decarboxylase and/or the vesicular inhibitory amino acid transporter respond to ATP or P(1),P(5)-di(adenosine-5') pentaphosphate (Ap(5)A) with an increase in the intrasynaptosomal calcium concentration measured by a microfluorimetric technique in single synaptic terminals. The ATP response 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 receptors, once activated in the presence of extrasynaptosomal calcium, induce a concentration-dependent GABA release from synaptosomal populations with EC(50) values of 16 and 20 microM for ATP and Ap(5)A, respectively. Specific inhibition of GABA release is obtained with pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (80 microM) on the ATP effect and with P(1),P(5)-di(inosine-5') pentaphosphate (100 nM) on the dinucleotide receptor.
Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
R
R
Gómez-Villafuertes
J
J
Gualix
M T
MT
Miras-Portugal
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D026905:Amino Acid Transport Systems; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000737:chemistry*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D026905:Amino Acid Transport Systems; D000906:Antibodies; D002352:Carrier Proteins; D015226:Dinucleoside Phosphates; D021122:Protein Subunits; D018048:Receptors, Purinergic P2; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D005968:Glutamate Decarboxylase; D002118:Calcium