Subtypes of excitatory amino acid receptors involved in the stimulation of [3H]dopamine release from cell cultures of rat ventral mesencephalon.
N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS), and kainic acid (KAIN), respective agonists for three excitatory amino acid (EAA) receptor subtypes, stimulated [3H]dopamine ([3H]DA) release from dissociated cell cultures of fetal rat ventral mesencephalon. Release evoked by all three agonists was Ca2(+)-dependent and inhibited by broad-spectrum antagonists (D,L-cis-2,3-piperidine dicarboxylic acid [PDA] and kynurenic acid [KYN]). However, both of these antagonists were more potent against KAIN than against QUIS and only KAIN-evoked release was blocked by gamma-D-glutamyl-aminomethyl sulfonic acid (GAMS, IC50 700 microM). NMDA-stimulated [3H]DA release was selectively inhibited by competitive (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid [CPP] and D,L-2-amino-5-phosphonovaleric acid [APV]) and non-competitive (phencyclidine and MK-801) NMDA receptor antagonists. In 1.2 mM Mg2+, NMDA-stimulated [3H]DA release was Na(+)-dependent and inhibited by tetrodotoxin (TTX, 2 microM) or by the local anaesthetic, lidocaine (200 microM). However, in 0 Mg 2+, NMDA-evoked release was not inhibited by TTX or lidocaine. Thus, TTX-sensitivity of the NMDA response in 1.2 mM Mg2+ apparently occurs because Na(+)-action potentials are required to alleviate a Mg2+ blockade. Neither QUIS- nor KAIN-evoked release was affected by Mg2+ or TTX. When extracellular NaCl was replaced by sucrose or Na2SO4, the QUIS response was increased. KAIN-evoked release was unaffected by the sucrose substitution and was attenuated in the Na2SO4-containing buffer. It is concluded that NMDA and QUIS/KAIN release [3H]DA via separate receptor subtypes.
Mount
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H
Department of Psychiatry, McGill University, Verdun, Quebec, Canada.
Quirion
R
R
Kohn-Alexander
J
J
Boksa
P
P
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000493:pharmacokinetics*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*
D010069:Oxadiazoles; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D007736:Kynurenic Acid; D008274:Magnesium; D004298:Dopamine