Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons.
Glutamate-induced excitotoxicity has been implicated as an important mechanism underlying a variety of brain injuries and neurodegenerative diseases. Previously we have shown that taurine has protective effects against glutamate-induced neuronal injury in cultured neurons. Here we propose that the primary underlying mechanism of the neuroprotective function of taurine is due to its action in preventing or reducing glutamate-induced elevation of intracellular free calcium, [Ca(2+)](i). This hypothesis is supported by the following findings. First, taurine transport inhibitors, e.g., guanidinoethyl sulfonate and beta-alanine, have no effect on taurine's neuroprotective function, suggesting that taurine protects against glutamate-induced neuronal damage through its action on the extracellular membranes. Second, glutamate-induced elevation of [Ca(2+)](i) is reduced to the basal level upon addition of taurine. Third, pretreatment of cultured neurons with taurine prevents or greatly suppresses the elevation of [Ca(2+)](i) induced by glutamate. Furthermore, taurine was found to inhibit the influx but not the efflux of (45)Ca(2+) in cultured neurons. Taurine has little effect on the binding of [(3)H]glutamate to the agonist binding site and of [(3)H]MDL 105,519 to the glycine binding site of the N-methyl-D-aspartic acid receptors, suggesting that taurine inhibits (45)Ca(2+) influx through other mechanisms, including its inhibitory effect on the reverse mode of the Na(+)/Ca(2+) exchangers (Wu et al. [2000] In: Taurine 4: taurine and excitable tissues. New York: Kluwer Academic/Plenum Publishers. p 35-44) rather than serving as an antagonist to the N-methyl-D-aspartic acid receptors.
Chen
W Q
WQ
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, USA.
Jin
H
H
Nguyen
M
M
Carr
J
J
Lee
Y J
YJ
Hsu
C C
CC
Faiman
M D
MD
Schloss
J V
JV
Wu
J Y
JY
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001927:Brain Diseases / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013654:Taurine / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium / Q000493:pharmacokinetics
D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D013654:Taurine; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D002118:Calcium