A 3,4-dihydroxyphenylalanine oxidation product is a non-N-methyl-D-aspartate glutamatergic agonist in rat cortical neurons.
Applications of solutions of 2,4,5-trihydroxyphenylalanine (TOPA or 6-hydroxyDOPA) to rat cortical neurons in culture monitored under whole-cell voltage clamp with patch electrodes resulted in currents which could be nearly completely blocked by the non-N-methyl-D-aspartate (non-NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but only weakly antagonized by the NMDA antagonist D.L-2-amino-5-phosphonovalerate (APV). Thus, TOPA can generate glutamatergic responses by interacting preferentially with non-NMDA receptors in cortical neurons. As these results show that a product closely related to the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA) has glutamatergic agonist properties, it is conceivable that catecholamine-containing brain areas may be at special risk for excitotoxic damage under certain conditions.
Aizenman
E
E
Department of Physiology, University of Pittsburgh School of Medicine, PA 15261.
White
W F
WF
Loring
R H
RH
Rosenberg
P A
PA
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats
D011810:Quinoxalines; C001388:6-hydroxydopa; D004295:Dihydroxyphenylalanine; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate