Cerebral taurine release mechanisms in vivo: pharmacological investigations in rats using microdialysis for proof of principle.
Cerebral taurine acts as neurotransmitter, as neuromodulator, or as osmoregulator. To investigate its release mechanisms in vivo, we combined the microdialysis technique with a variety of experimental paradigms. Taurine release was stimulated by either NMDA, NO or a hypotonic solution locally with or without the addition of the NMDA antagonists APV or Ketamine, or the NO synthase inhibitor L-NAME. Alternatively, the neuroprotective drug lubeluzole was applied i.v. NMDA, NO or the hypotonic solution stimulated the release of taurine. NMDA-mediated taurine release was inhibited by either APV, Ketamine or the NO synthase inhibitor L-NAME. Lubeluzole had no effect. Under the hypotonic conditions only lubeluzole was effective. These data confirm in vivo that the NMDA-induced taurine release is mediated via the NO cascade. By contrast, the release after a hypotonic stimulus is not related to the NO cascade. Instead, Na(+)- and/or Ca(2+)-mediated events might have been attenuated by lubeluzole.
Scheller
D
D
Janssen-Cilag GmbH, Drug Discovery, Neuss, Germany. dschelle@jacde.jnj.com
Korte
M
M
Szathmary
S
S
Tegtmeier
F
F
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism*; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D013654:Taurine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase