Pharmacological evidence for N-methyl-D-aspartate receptors on nigrostriatal dopaminergic nerve terminals.
The efflux of tritium from rat striatal synaptosomes labelled with [3H]dopamine was utilized as an index of dopamine (DA) release for the purpose of characterizing the receptors underlying the effects of L-glutamate. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA), and kainate each induced DA release in the absence of Mg2+, through NMDA was much more efficacious and only the NMDA response was inhibited by Mg2+. The response to L-glutamate was potentiated in a concentration-dependent manner by glycine. Further, it was completely inhibited by the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid and by the NMDA channel blocker phencyclidine. Finally, the response to L-glutamate was unaffected by either tetrodotoxin or the kainate-AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. These data demonstrate the presence of NMDA receptors on dopaminergic nerve terminals that mediate the ability of L-glutamate to release DA and suggest an additional mechanism by which information from the nigrostriatal and corticostriatal pathways may be integrated.
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
K M
KM
Johnson
Y J
YJ
Jeng
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D010879:Piperazines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008274:Magnesium; D010622:Phencyclidine; D005998:Glycine; D004298:Dopamine