Characterization of L-glutamate action on the release of endogenous dopamine from the rat caudate-putamen.
In the present study the effect of L-glutamic acid (L-Glu), N-methyl-D-aspartic acid (NMDA), kainic acid (KA) and quisqualic acid (QUIS) on the release of endogenous dopamine (DA) from slices of the rat caudate-putamen was investigated. DA was measured by high-performance liquid chromatography coupled to an electrochemical detector. L-Glu, NMDA, KA and QUIS, in the absence of Mg++, produced a dose-related, Ca++-dependent increase in DA release. The order of agonist efficacy was L-Glu greater than NMDA greater than KA = QUIS. D-2-amino-7-phosphonoheptanoic acid (0.5 mM), but not L-2-amino-7-phosphonoheptanoic acid, antagonized the action of L-Glu and NMDA, but did not modify the effect of KA or QUIS. Tetrodotoxin (0.1 microM) partially inhibited the stimulatory effect of KA and QUIS, but not that of L-Glu or NMDA. Mg++ (1.2 mM) abolished the excitatory effect of NMDA, significantly reduced the action of L-Glu, but did not influence the action of KA or QUIS. The inhibitory action of Mg++ on the L-Glu-induced DA release was reversed when L-Glu was coupled to high concentrations of K+. N-allylnormetazocine (SKF-10,047), a benzmorphan agent, produced a stereospecific inhibition of L-Glu-induced DA release. This inhibition was also produced by 1-[1-(2-thienyl)cyclohexyl]piperidine, a phencyclidine receptor ligand, but not by 1,3-di-O-tolylguanidine, a sigma receptor-selective ligand. The results of this study show that L-Glu increases DA release predominantly by activation of the NMDA receptor located presynaptically on dopaminergic afferents.(ABSTRACT TRUNCATED AT 250 WORDS)
Clow
D W
DW
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Jhamandas
K
K
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects
D000596:Amino Acids; D005971:Glutamates; D010069:Oxadiazoles; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; C012134:SK&F 10047; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D008274:Magnesium; D010620:Phenazocine; C031231:2-amino-7-phosphonoheptanoic acid; D011188:Potassium; D004298:Dopamine