SULFUR-CONTAINING AMINO-ACIDS MODULATE NORADRENALINE RELEASE FROM HIPPOCAMPAL SLICES

The L- and D-enantiomers of the sulphur-containing amino acids (SAAs)- homocysteate, homocysteine sulphinate, cysteate, cysteine sulphinate, and S-sulphocysteine-stimulated [H-3]noradrenaline release from rat hi ppocampal slices in a concentration-dependent manner, The relative pot encies of the L-isomers (EC(50) values of 1.05-1.96 mM) were of simila r order to that of glutamate (1.56 mM), which was 10-fold lower than t hat of NMDA (0.15 mM), whereas the D-isomers exhibited a wider range o f potencies (0.75 to >5 mM). All stimulatory effects of the SAAs were significantly inhibited by the voltage-sensitive Nai channel blocker t etrodotoxin (55-71%) and completely blocked by addition of Mg2+ or Co2 + to the incubation medium. All SAA-evoked responses were concentratio n-dependently antagonized by the selective NMDA receptor antagonist D- (-)-2-amino-5-phosphonopentanoic acid (IC50 values of 3.2-49.5 mu M). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antag onist, at 100 mu M inhibited the [H-3]noradrenaline release induced by glutamate and NMDA (65 and 76%, respectively) and by all SAAs studied (65-85%), whereas 10 mu M CNQX only inhibited the effects of S-sulpho -L-cysteine and L- and D-homocysteate (33, 32, and 44%, respectively), However, the more selective AMPA/kainic acid receptor antagonist 6-ni tro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (100 mu M), which did no t antagonize the [H-3]noradrenaline release induced by glutamate and N MDA, reduced only the S-sulpho-L-cysteine-evoked response (25%). Thus, the stimulation of Ca2+-dependent [H-3] noradrenaline release from hi ppocampal slices elicited by the majority of the SAAs appears to be me diated by the NMDA receptor.