N‐Methyl‐d‐aspartate receptors mediating hippocampal noradrenaline and striatal dopamine release display differential sensitivity to quinolinic acid, the HIV‐1 envelope protein gp120, external pH and protein kinase C inhibition

• Published in: Journal of neurochemistry Vol. 76; no. 1; pp. 139 - 148
• Main Authors: Pittaluga, Anna, Pattarini, Roberto, Feligioni, Marco, Raiteri, Maurizio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2001; Blackwell
• Subjects: Animals; Aspartic Acid - metabolism; Aspartic Acid - pharmacology; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Corpus Striatum - chemistry; Corpus Striatum - metabolism; Dopamine - metabolism; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Glycine - metabolism; Glycine - pharmacology; gp120; Hippocampus - chemistry; Hippocampus - metabolism; HIV Envelope Protein gp120 - pharmacology; Human immunodeficiency virus; Human immunodeficiency virus 1; Hydrogen-Ion Concentration; Male; N-Methylaspartate - metabolism; N-Methylaspartate - pharmacology; NMDA receptor subtypes; Norepinephrine - metabolism; NR1 subunit variants; Piperidines - pharmacology; protein kinase C; Protein Kinase C - antagonists & inhibitors; quinolinic acid; Quinolinic Acid - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Serine - metabolism; Serine - pharmacology; Synaptosomes - chemistry; Synaptosomes - drug effects; Synaptosomes - metabolism; Vertebrates: nervous system and sense organs; Zinc - pharmacology; Protein kinase C; Dopamine; Rat; Enzyme; Transferases; Rodentia; Central nervous system; Glutamate receptor; Corpus striatum; Catecholamine; Subunit; Vertebrata; Sensitivity; Mammalia; Norepinephrine; NMDA receptor; Hippocampus; Release; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00057.x

NMDA receptors regulating hippocampal noradrenaline (NA) and striatal dopamine (DA) release have been compared using superfused synaptosomes prelabelled with the [3H]catecholamines. Both receptors mediated release augmentation when exposed to NMDA plus glycine. Quinolinic acid (100 µm or 1 mm) plus glycine (1 µm)‐elicited [3H]NA, but not [3H]DA release. The NMDA (100 µm)‐evoked release of [3H]NA and [3H]DA was similar and concentration‐dependently enhanced by glycine or d‐serine (0.1–1 µm); in contrast, the HIV‐1 envelope protein gp120 potently (30–100 pm) enhanced the NMDA‐evoked release of [3H]NA, but not that of [3H]DA. Gp120 also potentiated quinolinate‐evoked [3H]NA release. Ifenprodil (0.1–0.5 µm) or CP‐101,606 (0.1–10 µm) inhibited the NMDA plus glycine‐evoked release of both [3H]catecholamines. Zinc (0.1–1 µm) was ineffective. Lowering external pH from 7.4 to 6.6 strongly inhibited the release of [3H]NA elicited by NMDA plus glycine, whereas the release of [3H]DA was unaffected. The protein kinase C inhibitors GF 109203X (0.1 µm) or H7 (10 µm) selectively prevented the effect of NMDA plus glycine on the release of [3H]NA. GF 109203X also blocked the release of [3H]NA induced by NMDA or quinolinate plus gp120. It is concluded that the hippocampal NMDA receptor and the striatal NMDA receptor are pharmacologically distinct native subtypes, possibly containing NR2B subunits but different splice variants of the NR1 subunit.