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 hippocampal slices in a concentration-dependent manner, The relative potencies of the L-isomers (EC(50) values of 1.05-1.96 mM) were of similar order to that of glutamate (1.56 mM), which was 10-fold lower than that of NMDA (0.15 mM), whereas the D-isomers exhibited a wider range of potencies (0.75 to >5 mM). All stimulatory effects of the SAAs were significantly inhibited by the voltage-sensitive Nai channel blocker tetrodotoxin (55-71%) and completely blocked by addition of Mg2+ or Co2+ to the incubation medium. All SAA-evoked responses were concentration-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 antagonist, 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-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (100 mu M), which did not antagonize the [H-3]noradrenaline release induced by glutamate and NMDA, reduced only the S-sulpho-L-cysteine-evoked response (25%). Thus, the stimulation of Ca2+-dependent [H-3] noradrenaline release from hippocampal slices elicited by the majority of the SAAs appears to be mediated by the NMDA receptor.</p
