Striatal NMDA receptor subtypes: the pharmacology of N-methyl-D-aspartate-evoked dopamine, gamma-aminobutyric acid, acetylcholine and spermidine release.
We have examined the inhibitory potencies of MK 801, memantine, dextromethorphan, Mg2+ and of strychnine-insensitive glycine site antagonists on the N-methyl-D-aspartate (NMDA)-evoked (300 microM) release of [14C]acetylcholine and [3H]spermidine or [14C] gamma-aminobutyric acid [14C]GABA and [3H]dopamine from rat striatal slices. MK 801, dextromethorphan and all glycine antagonists examined (7-chlorokynurenate, L-689,560 ((+/-)-trans-2-carboxy-5,7-dichlorotetrahydroquinoline-4-phenylure a), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dichloroquinoxaline-2,3-dione (DNQX), and (+)-HA966 ((3-amino-1-hydroxypyrrolidin-2-one) more potently inhibited NMDA-evoked dopamine and GABA release than acetylcholine and spermidine release by a factor of 3-21. MgCl2, which does not inhibit NMDA-evoked spermidine release, and memantine which only weakly antagonised NMDA-evoked spermidine release, inhibited NMDA-evoked dopamine, acetylcholine and GABA release with similar potencies. No pharmacological differences were observed between NMDA-evoked dopamine and GABA release. These findings extend those suggesting that NMDA-evoked acetylcholine and spermidine release are mediated by different NMDA receptor subtypes in the striatum and suggest a third native subtype with a distinct pharmacology that regulates striatal dopamine and GABA release.
Nankai
M
M
Synthélabo Recherche, Rueil-Malmaison, France.
Fage
D
D
Carter
C
C
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013095:Spermidine / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D009125:Muscle Relaxants, Central; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D001120:Arginine; D003620:Dantrolene; D013095:Spermidine