Potentiation of N-methyl-D-aspartate-stimulated dopamine release from rat brain slices by aluminum fluoride and carbachol.
N-Methyl-D-aspartate (NMDA) stimulated the release of endogenous dopamine from striatal slices prepared from adult Sprague-Dawley rats. A mixture of sodium fluoride and aluminum chloride (AlF4-) added to the slices significantly potentiated the NMDA-stimulated release of dopamine in a concentration- and time-dependent manner. The AlF4- mixture had no effect on the nonstimulated basal efflux of dopamine, and no increases in NMDA-stimulated release were observed when NaF was replaced with NaCl. Similarly, AlCl3 or a mixture of NaCl and AlCl3 had no effect on NMDA-stimulated release. The AlF(4-)-induced increase in NMDA-stimulated dopamine release was totally blocked by magnesium or the selective NMDA glycine antagonist 7-chlorokynurenic acid. Striatal slices depolarized with KCl (15 mM) also released dopamine and this release was similarly potentiated by AlF4-. However, KCl-stimulated dopamine release from striatal synaptosomes was not potentiated by concentrations of AlF4- that greatly increased release from striatal slices. NMDA did not stimulate the release of dopamine from striatal synaptosomes in the absence or presence of aluminum fluoride. Modulators of adenylate cyclase (forskolin) and protein kinase C (phorbol esters) did not enhance NMDA-stimulated dopamine release. The protein kinase C inhibitor H-7 also did not reduce the potentiating effects of AlF4-. The mixed cholinergic agonist carbachol and the calcium ionophore A23187 mimicked the AlF4- effect although the increase in NMDA-stimulated dopamine release produced by these agents was less than that seen with AlF4-.(ABSTRACT TRUNCATED AT 250 WORDS)
Woodward
J J
JJ
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Harms
J
J
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology
D017607:Aluminum Compounds; D002147:Calmodulin; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; D016202:N-Methylaspartate; C017967:W 7; D002217:Carbachol; D000535:Aluminum; D019204:GTP-Binding Proteins; D005459:Fluorides; D004298:Dopamine; C032311:aluminum fluoride