{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:55:50Z","timestamp":1788339350932,"version":"build-2803163510"},"reference-count":64,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2001,12,1]]},"abstract":"<jats:p> In the course of studying the hypertonicity-activated ion transporters in Xenopus oocytes, we found that activation of endogenous oocyte Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchange activity (xoNHE) by hypertonic shrinkage required Cl<jats:sup>\u2212<\/jats:sup>, with an EC<jats:sub>50<\/jats:sub> for bath [Cl<jats:sup>\u2212<\/jats:sup>] of \u223c3 mM. This requirement for chloride was not supported by several nonhalide anions and was not shared by xoNHE activated by acid loading. Hypertonicity-activated xoNHE exhibited an unusual rank order of inhibitory potency among amiloride derivatives and was blocked by Cl<jats:sup>\u2212<\/jats:sup> transport inhibitors. Chelation of intracellular Ca<jats:sup>2+<\/jats:sup> by injection of EGTA blocked hypertonic activation of xoNHE, although many inhibitors of Ca<jats:sup>2+<\/jats:sup>-related signaling pathways were without inhibitory effect. Hypertonicity activated oocyte extracellular signal-regulated kinase 1\/2 (ERK1\/2), but inhibitors of neither ERK1\/2 nor p38 prevented hypertonic activation of xoNHE. However, hypertonicity also stimulated a Cl<jats:sup>\u2212<\/jats:sup>-dependent increase in c-Jun NH<jats:sub>2<\/jats:sub>-terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE but not activation by acid loading. We conclude that hypertonic activation of Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchange in Xenopusoocytes requires Cl<jats:sup>\u2212<\/jats:sup> and is mediated by activation of JNK. <\/jats:p>","DOI":"10.1152\/ajpcell.2001.281.6.c1978","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:37:13Z","timestamp":1514147833000},"page":"C1978-C1990","source":"Crossref","is-referenced-by-count":29,"title":["Role of JNK in hypertonic activation of Cl<sup>\u2212<\/sup>-dependent  Na<sup>+<\/sup>\/H<sup>+<\/sup> exchange in <i>Xenopus <\/i>oocytes"],"prefix":"10.1152","volume":"281","author":[{"given":"Greg G.","family":"Goss","sequence":"first","affiliation":[{"name":"Department of Biological Science, University of Alberta, Edmonton, Alberta, Canada T6G 2E9,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Molecular Medicine and Renal Units, Beth Israel 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