STIMULATION OF NORADRENALINE RELEASE IN HUMAN CEREBRAL-CORTEX MEDIATED BY N-METHYL-D-ASPARTATE (NMDA) AND NON-NMDA RECEPTORS

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 [H-3]-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. 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.