{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:20:59Z","timestamp":1777580459808,"version":"3.51.4"},"reference-count":60,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p> Central neurons are extremely vulnerable to hypoxic\/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that \u03b4-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia\/ischemia disrupts ionic homeostasis with an increase in extracellular K<jats:sup>+<\/jats:sup>, which plays a role in neuronal death, we asked whether DOR activation preserves K<jats:sup>+<\/jats:sup> homeostasis during hypoxic\/ischemic stress. To test this hypothesis, extracellular recordings with K<jats:sup>+<\/jats:sup>-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen\u2013glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala<jats:sup>2<\/jats:sup>, D-Leu<jats:sup>5<\/jats:sup>]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K<jats:sup>+<\/jats:sup> and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K<jats:sup>+<\/jats:sup> and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K<jats:sup>+<\/jats:sup> homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K<jats:sup>+<\/jats:sup> homeostasis during anoxia or ischemia. <\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600352","type":"journal-article","created":{"date-parts":[[2006,6,14]],"date-time":"2006-06-14T11:54:41Z","timestamp":1150286081000},"page":"356-368","source":"Crossref","is-referenced-by-count":57,"title":["Cortical \u03b4-Opioid Receptors Potentiate K<sup>+<\/sup> Homeostasis During Anoxia and Oxygen\u2013Glucose Deprivation"],"prefix":"10.1177","volume":"27","author":[{"given":"Dongman","family":"Chao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Respiratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Respiratory Medicine, Yale 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