Stimulation of noradrenaline release in human cerebral cortex mediated by N-methyl-D-aspartate (NMDA) and non-NMDA receptors.

Article date: 1992/5/1

PubMed ID: 1674916

Journal name: British journal of pharmacology (ISSN: 0007-1188)


1. Human brain cortical slices from patients undergoing neurosurgery for treatment of epilepsy resistant to antiepileptic drugs were used to identify and characterize N-methyl-D-aspartate (NMDA) and non-NMDA receptors mediating stimulation of noradrenaline release. The slices preincubated with [3H]-noradrenaline were superfused with Krebs-Henseleit solution with or without Mg2+ (1.2 mmol l-1) and were stimulated by 2-min exposure to NMDA, kainic acid or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 2. In slices superfused without Mg2+, NMDA induced a concentration-dependent tritium overflow. 3. The NMDA-evoked tritium overflow was almost abolished by tetrodotoxin (TTX), Mg2+ or by omission of Ca2+ from the superfusion fluid. 2-Amino-5-phosphonopentanoic acid (AP5; a competitive NMDA receptor antagonist) or dizocilpine (formerly MK-801; an antagonist at the phencyclidine receptor within the NMDA-gated ion channel) inhibited the NMDA-evoked tritium overflow. The stimulatory effect of NMDA was not significantly enhanced by glycine added to the superfusion fluid but was reduced by 7-chlorokynurenic acid (an antagonist at the glycine site coupled to the NMDA receptor). 4. In slices superfused with solution containing Mg2+, kainic acid or AMPA induced a concentration-dependent tritium overflow which was susceptible to blockade by TTX. 5. The kainic acid-evoked tritium overflow was not affected by DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP37849; a competitive NMDA receptor antagonist), but was inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; an antagonist at glutamate receptors of the non-NMDA type). 6. The AMPA-evoked tritium overflow was also inhibited by CNQX.2ń

Author List: Fink K, Schultheiss R, Göthert M

Publication Types: Journal Article

Substances mentioned in the article: Quinoxalines; Receptors, N-Methyl-D-Aspartate; Tritium; 2-amino-4-methyl-5-phosphono-3-pentenoic acid; Ibotenic Acid; Tetrodotoxin; N-Methylaspartate; Dizocilpine Maleate; 6-Cyano-7-nitroquinoxaline-2,3-dione; 2-Amino-5-phosphonovalerate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kynurenic Acid; Magnesium; 7-chlorokynurenic acid; Kainic Acid; Glycine; Norepinephrine;

Mesh terms: 2-Amino-5-phosphonovalerate/analogs & derivatives; 6-Cyano-7-nitroquinoxaline-2,3-dione; Adult; Cerebral Cortex/drug effects; Dizocilpine Maleate/pharmacology; Dose-Response Relationship, Drug; Female; Glycine/pharmacology; Humans; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; Kynurenic Acid/analogs & derivatives; Magnesium/pharmacology; Male; N-Methylaspartate/antagonists & inhibitors; Norepinephrine/metabolism; Quinoxalines/pharmacology; Receptors, N-Methyl-D-Aspartate/metabolism; Tetrodotoxin/pharmacology; Tritium/metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

Citations: - 14389

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