Regulatory role of nitric oxide over extracellular taurine in the hippocampus of freely moving rats.
We have studied the effects of drugs which manipulate nitric oxide (NO) levels as well the effect of N-methyl-d-aspartate (NMDA) infusion on extracellular taurine in rat hippocampus using in vivo microdialysis. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) increased dialysate taurine in a concentration-dependent manner, and this effect was blocked by the inhibitor of soluble guanylate cyclase1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ). NMDA (100 microM) increased hippocampal taurine release, an effect that was reversed by the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 10 microM). The non-selective nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (L-NAME; 100 microM and 1.0 mM) increased extracellular taurine in a concentration-dependent manner while 7-nitroindazole (7-NI), a relatively selective neuronal NOS (nNOS) inhibitor, at the same concentrations decreased extracellular taurine. L-NAME (1.0 mM) infused prior to NMDA did not alter the effect of NMDA on extracellular taurine having an effect essentially identical to that seen with L-NAME infused alone. In contrast, when 7-NI was infused for 30 min prior to NMDA, taurine levels were no longer increased above basal. This suggests to us that taurine efflux is mediated by two different mechanisms: an NMDA-evoked, 7-NI-sensitive pathway which may be dependent on cyclic guanosine monophosphate formation, and an L-NAME-modulated mechanism which presumably involves other members of the NOS group of enzymes than nNOS alone.
Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK.
Jo
J
Watts
Joanna
J
Segieth
Brian
B
Pearce
Peter S
PS
Whitton
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D017551:Microdialysis / Q000379:methods; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D013654:Taurine; D009569:Nitric Oxide; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D010396:Penicillamine