Sulphur-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 [3H]noradrenaline release from rat hippocampal slices in a concentration-dependent manner. The relative potencies of the L- isomers (EC50 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 Na+ 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 3.249.5 μM). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non- NMDA receptor antagonist, at 100 μM inhibited the [3H]noradrenaline release induced by glutamate and NMDA (65 and 76%, respectively) and by all SAAs studied (65-85%), whereas 10 μM 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 μM), which did not antagonize the [3H]noradrenaline release induced by glutamate and NMDA, reduced only the S-sulpho-L-cysteine-evoked response (25%). Thus, the stimulation of Ca2+-dependent [3H] noradrenaline release from hippocampal slices elicited by the majority of the SAAs appears to be mediated by the NMDA receptor