title: Cerebral taurine release mechanisms in vivo: pharmacological investigations in rats using microdialysis for proof of principle.
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 Ca(2+)-mediated events might have been attenuated by lubeluzole.
authors.affiliation: Janssen-Cilag GmbH, Drug Discovery, Neuss, Germany. dschelle@jacde.jnj.com
authors.forename: D
authors.initials: D
authors.lastname: Scheller
authors.forename: M
authors.initials: M
authors.lastname: Korte
authors.forename: S
authors.initials: S
authors.lastname: Szathmary
authors.forename: F
authors.initials: F
authors.lastname: Tegtmeier
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D013654:Taurine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase