Sulphur-containing amino acids modulate noradrenaline release from hippocampal slices

J Neurochem. 1997 Apr;68(4):1534-41. doi: 10.1046/j.1471-4159.1997.68041534.x.

Abstract

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 3.2 - 49.5 microM). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, at 100 microM inhibited the [3H]noradrenaline release induced by glutamate and NMDA (65 and 76%, respectively) and by all SAAs studied (65-85%), whereas 10 microM 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 microM), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Amino Acids, Sulfur / chemistry
  • Amino Acids, Sulfur / pharmacology*
  • Animals
  • Calcium / pharmacology
  • Cobalt / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Magnesium / pharmacology
  • Male
  • N-Methylaspartate / pharmacology
  • Norepinephrine / metabolism*
  • Norepinephrine / pharmacology
  • Organ Culture Techniques
  • Rats
  • Rats, Wistar
  • Sensitivity and Specificity
  • Stereoisomerism
  • Tetrodotoxin / pharmacology
  • Tritium

Substances

  • Amino Acids, Sulfur
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Tritium
  • Cobalt
  • Tetrodotoxin
  • N-Methylaspartate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Magnesium
  • Calcium
  • Norepinephrine