Characteristics of hippocampal glycine release in cell-damaging conditions in the adult and developing mouse.
The release of preloaded [3H]glycine from hippocampal slices from 7-day-old and 3-month-old (adult) mice was studied in different cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress and the presence of free radicals and metabolic poisons, using a superfusion system. Glycine release was greatly enhanced in all the above conditions in both age groups, with the exception of hypoxia in developing mice. This coincides with the increased susceptibility to seizures and excitotoxicity during postnatal development. The ischemia-induced release of glycine was Ca2+-independent at both ages. The release was potentiated by exogenously applied glycine but not in Na+-free conditions, indicating the involvement of Na+-dependent transporters operating outwards. The Cl- channel blockers 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonate and diisothiocyanostilbene-2,2'-disulphonate generally reduced the ischemia-induced release, suggesting that this occurs through anion channels in both developing and adult mice. Furthermore, in the adult hippocampus riluzole and amiloride inhibited the release, indicating that Na+ channels also contribute to the ischemia-evoked release. Since glycine is an essential factor in glutamate-induced Ca2+ channel opening at the N-methyl-D-aspartate receptor, the elevated levels of glycine, together with the increased release of excitatory amino acids, must obviously collaborate in the development of ischemic neuronal damage.
Saransaari
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Tampere Brain Research Center, Medical School, University of Tampere, Finland. blpisa@uta.fi
Oja
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D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007003:Hypoglycemia / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000502:physiology
D007473:Ion Channels; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005998:Glycine