Mechanisms of ischemia-induced taurine release in mouse hippocampal slices.
Taurine release in the hippocampus is markedly potentiated in various cell-damaging conditions, including ischemia and excitotoxic damage produced by glutamate. The increase in the levels of taurine may provide an important protective mechanism against excitotoxicity. The mechanisms of the enhanced release were now studied in mouse hippocampal slices using a superfusion system. The basal release of [3H]taurine was significantly increased in Na+-deficient media in normal conditions, whereas the ischemia-evoked release was decreased, indicating the participation of Na+-dependent transport processes. The involvement of taurine transport carriers in the release was confirmed with the structural analogs, hypotaurine and beta-alanine. These amino acids potentiated the release by trans-stimulation in normoxia. In Na+-free conditions, this heteroexchange was not discernible, the carriers not being functional without Na+. In ischemia, the marked potentiation of taurine release by hypotaurine and beta-alanine further indicates that the Na+-requiring transporters also operate in ischemia. The effects of membrane disruption on taurine release due to activation of phospholipases were estimated using phospholipase and protein kinase inhibitors, which had no marked effects on hippocampal taurine release. The chloride channel blockers, 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulphonate (SITS) and diisothiocyanostilbene-2,2'-disulphonate (DIDS), reduced the ischemia-induced release, suggesting that taurine diffusion through an anion channel is partially responsible for the enhanced release in ischemia.
Tampere Brain Research Center, University of Tampere Medical School, Box 607, FIN-33101, Tampere, Finland. blpisa@uta.fi
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Saransaari
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Oja
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D066298:In Vitro Techniques; D017136:Ion Transport; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010477:Perfusion; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D012964:Sodium / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000502:physiology; D013654:Taurine / Q000378:metabolism*
D004791:Enzyme Inhibitors; D015222:Sodium Channels; D013654:Taurine; D012964:Sodium; D010770:Phosphotransferases; D010740:Phospholipases