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Cerebral Taurine Release Mechanisms In Vivo: Pharmacological Investigations in Rats Using Microdialysis for Proof of Principle
Authors:Dieter Scheller  Martin Korte  Stefan Szathmary  Frank Tegtmeier
Affiliation:(1) Drug Discovery, Janssen-Cilag GmbH, Raiffeisenstr. 8, D-41470 Neuss, Germany;(2) Max-Planck-Institut für Neurobiologie, Am Klopferspitz 18a, 82152 Martinsried, Germany;(3) Drug Discovery, Janssen-Cilag GmbH, Raiffeisenstr. 8, D-41470 Neuss, Germany
Abstract: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 Ca2+- mediated events might have been attenuated by lubeluzole.
Keywords:Cerebral cortex  microdialysis  taurine  NMDA  spreading depression  hypotonic solution
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