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Stimulation of noradrenaline release in human cerebral cortex mediated by N‐methyl‐ d ‐aspartate (NMDA) and non‐NMDA receptors
Author(s) -
Fink Klaus,
Schultheiß Rolf,
Göthert Manfred
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14294.x
Subject(s) - nmda receptor , ampa receptor , kainic acid , cnqx , phencyclidine , 2 amino 5 phosphonovalerate , chemistry , competitive antagonist , long term depression , dizocilpine , glutamate receptor , tetrodotoxin , kainate receptor , antagonist , pharmacology , receptor , biophysics , biology , biochemistry , excitatory amino acid antagonists
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 [ 3 H]‐noradrenaline were superfused with Krebs‐Henseleit solution with or without Mg 2+ (1.2 mmol 1 −1 ) and were stimulated by 2‐min exposure to NMDA, kainic acid or (RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). 2 In slices superfused without Mg 2+ , NMDA induced a concentration‐dependent tritium overflow. 3 The NMDA‐evoked tritium overflow was almost abolished by tetrodotoxin (TTX), Mg 2+ or by omission of Ca 2+ 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 Mg 2+ , 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. 7 It is concluded that NMDA receptors as well as kainate‐ and AMPA‐recognizing non‐NMDA receptors stimulate noradrenaline release in the human brain cortex.