Effect of L-homocysteine and derivatives on the high-affinity uptake of taurine and GABA into synaptosomes and cultured neurons and astrocytes.
The effect of L-homocysteine and selected derivatives on the high-affinity uptake of the inhibitory neuroeffectors, GABA and taurine, was investigated in synaptosomes, and in cultured neurons and astrocytes. High-affinity uptake of taurine into synaptosomes was inhibited most effectively by L-homocysteine, DL-homocysteine and homocystine whereas neuronal uptake was unaffected by any of the compounds tested. The high affinity uptake of taurine into astrocytes was markedly inhibited by L-homocysteine, L-homocysteic acid and L-homocystine. High-affinity GABA uptake into astrocytes was notably inhibited by L-homocystine, none of the other compounds tested causing appreciable inhibition below a concentration of 5 mM. Neuronal and synaptosomal high-affinity uptake of GABA was not significantly affected by any of the test compounds at concentrations below 5 mM. The implication of these results to the study of the mechanism of homocysteine-induced seizures and their relevance to the genetic disorder homocystinuria is discussed.
Allen
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IC
Department of Biochemistry and Microbiology, University of St. Andrews, Fife, Scotland, U.K.
Schousboe
A
A
Griffiths
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R
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D004622:Embryo, Mammalian; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D006710:Homocysteine; D013654:Taurine; D005680:gamma-Aminobutyric Acid