High glutamate concentrations evoke Ca(++)-independent dopamine release from striatal slices: a possible role of reverse dopamine transport.
Glutamate stimulated the efflux of dopamine from slices of rat striatum superfused with a Krebs' bicarbonate buffer containing a physiological concentration of Mg++ (1.2 mM). This effect was observed in the presence of high concentrations of glutamate (3-10 mM), but not at lower concentrations (0.01-1 mM). The response was not accompanied by increased lactate dehydrogenase activity, a measure of glutamate neurotoxicity. At 10 mM, glutamate increased dopamine efflux by more than 9-fold. This was reduced to about 34% of the control response by either the competitive N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid (100 microM) or the noncompetitive N-methyl-D-aspartate receptor antagonist MK 801 [(+)-5-methyl-10,11-dihydro-5H-dibenso[a,d]cyclohepten-5,10- imine hydrogen maleate] (1-10 microM), but was unaffected by a kainate/quisqualate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10-100 microM). Glutamate-stimulated dopamine efflux also was unaffected by tetrodotoxin (0.5 microM), withdrawal of extracellular Ca++ [and addition of 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid] or systemic administration of reserpine (5 mg/kg, 24 hr before the experiment), an inhibitor of the vesicular storage of dopamine. In contrast, nomifensine (10 microM), an inhibitor of high-affinity dopamine transport, reduced glutamate-induced dopamine efflux to 15% of the control response. Moreover, the response to glutamate was blocked by deleting NaCl from the medium. Collectively, these results suggest that, at high concentrations and in the presence of Mg++, glutamate can stimulate the release of dopamine by a mechanism that does not use Ca(++)-dependent exocytosis but instead involves a reversal of the dopamine transport system.(ABSTRACT TRUNCATED AT 250 WORDS)
Lonart
G
G
Department of Behavioral Neuroscience, University of Pittsburgh, Pennsylvania.
Zigmond
M J
MJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005971:Glutamates / Q000493:pharmacokinetics / Q000494:pharmacology*; D018698:Glutamic Acid; D008274:Magnesium / Q000502:physiology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology
D005971:Glutamates; D009627:Nomifensine; D018698:Glutamic Acid; D012110:Reserpine; D008274:Magnesium; D002118:Calcium; D004298:Dopamine