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The advent of flame photometry and tracer techniques brought Na<jats:sup>+<\/jats:sup> to the fore, especially since short\u2010circuited frog skin (<jats:italic>Rana temporaria<\/jats:italic>) produces baseline net movement of Na<jats:sup>+<\/jats:sup> and not of Cl<jats:sup>\u2212<\/jats:sup>. Zadunaisky was among the first to describe what is currently termed secondary active Cl<jats:sup>\u2212<\/jats:sup> transport, helping stimulate interest in Cl<jats:sup>\u2212<\/jats:sup> handling by other tissues, notably the thick ascending limb of the loop of Henle important in renal counter\u2010current multiplication. More recently, molecules responsible for electroneutral and electrogenic Cl<jats:sup>\u2212<\/jats:sup> transfer have been cloned, and specific diseases resulting from their faulty expression have been identified. The clinical importance of transepithelial Cl<jats:sup>\u2212<\/jats:sup> transfer is illustrated by studies of aqueous humor formation by the eye's bilayered ciliary epithelium. NaCl is taken up from the stroma by the pigmented ciliary epithelial (PE) layer, diffuses through gap junctions into the nonpigmented ciliary epithelial (NPE) layer, and is released into the aqueous humor largely through Na<jats:sup>+<\/jats:sup> pumps and Cl<jats:sup>\u2212<\/jats:sup> channels. ATP released by NPE cells can be ecto\u2010enzymatically metabolized to adenosine. Adenosine can mediate paracrine\/autocrine stimulation of Cl<jats:sup>\u2212<\/jats:sup> channels and aqueous humor secretion by occupying A<jats:sub>3<\/jats:sub> adenosine receptors (ARs). A<jats:sub>3<\/jats:sub>AR agonists indeed elevate, and A<jats:sub>3<\/jats:sub>AR antagonists lower, intraocular pressure (IOP) in wild\u2010type mice. A<jats:sub>3<\/jats:sub>AR knockout mice have low IOP and their responses to A<jats:sub>3<\/jats:sub>AR agonists and antagonists are blunted; this suggests that reducing Cl<jats:sup>\u2212<\/jats:sup>\u2010channel activity with A<jats:sub>3<\/jats:sub>AR antagonists may provide a novel approach for treating glaucoma. <jats:italic>J. Exp. Zool. 300A:5\u201313, 2003<\/jats:italic>. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jez.a.10303","type":"journal-article","created":{"date-parts":[[2003,10,30]],"date-time":"2003-10-30T11:26:28Z","timestamp":1067513188000},"page":"5-13","source":"Crossref","is-referenced-by-count":17,"title":["The fall and rise of active chloride transport: Implications for regulation of intraocular pressure"],"prefix":"10.1002","volume":"300A","author":[{"given":"Mortimer M.","family":"Civan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,10,29]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0002-9394(00)00538-9","article-title":"The advanced glaucoma intervention study (AGIS): 7. 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