Role of NMDA, AMPA and kainate receptors in mediating glutamate- and 4-AP-induced dopamine and acetylcholine release from rat striatal slices.
Striatal slices, preincubated with [3H]dopamine and [14C]choline, were superfused continuously and subjected to electrical field stimulation (3 Hz) and perfused with amino acid analogues or 4-amino pyridine (4-AP). The released radioactivity was used to monitor release of the neurotransmitters dopamine (DA) and acetylcholine (ACh). Glutamate, NMDA (in the absence of Mg2+), AMPA, kainic acid, domoate and 4-AP all induced DA and ACh release in a concentration-dependent manner. The DA and ACh release induced by NMDA (15 microM) and glutamate (1 mM) was essentially abolished by Mg2+ (1.15 mM), whereas release induced by AMPA (100 microM), kainic acid (100 microM) or 4-AP (30 microM) was not reduced. Tetrodotoxin (1 microM) essentially abolished the effects of NMDA, markedly reduced the effects of glutamate, AMPA and 4-AP, whereas the effect of kainic acid was only modestly affected. MK-801 (30 nM) reduced NMDA-induced DA release by some 70% and ACh release by 30%. MK-801 reduced 4-AP-induced DA release by 40% but not ACh release. CNQX in a concentration (10 microM) that scarcely affected NMDA-induced ACh release, but blocked that induced by AMPA, kainic acid or domoate, reduced the ACh release induced by 4-AP. In summary, DA and ACh release from rat striatum can be stimulated by activation of NMDA and non-NMDA glutamate receptors, and this mechanism is activated by the potassium channel blocker 4-AP.
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
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D015761:4-Aminopyridine / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D018846:Excitatory Amino Acids / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D015761:4-Aminopyridine; D000109:Acetylcholine; D004298:Dopamine; D018846:Excitatory Amino Acids; D018698:Glutamic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate