Sulphur-Containing Amino Acids Modulate Noradrenaline Release from Hippocampal Slices |
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Authors: | G Selema R M Cristòfol S Gassó R Griffiths E Rodríguez-Farré |
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Institution: | Department of Pharmacology and Toxicology, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, Spain;and; Neurochemistry Group, Division of Cell and Molecular Biology, University of St. Andrews, St. Andrews, Fife, Scotland |
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Abstract: | 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 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+-dependent3H]noradrenaline release from hippocampal slices elicited by the majority of the SAAs appears to be mediated by the NMDA receptor. |
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Keywords: | Noradrenaline release Sulphur-containing amino acids Excitatory amino acid receptors Hippocampal slices Rat |
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