{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:50:08Z","timestamp":1791960608183,"version":"4.3.4"},"reference-count":35,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2001,11,1]]},"abstract":"<jats:p> Purines regulate intraocular pressure. Adenosine activates Cl<jats:sup>\u2212<\/jats:sup> channels of nonpigmented ciliary epithelial cells facing the aqueous humor, enhancing secretion. Tamoxifen and ATP synergistically activate Cl<jats:sup>\u2212<\/jats:sup> channels of pigmented ciliary epithelial (PE) cells facing the stroma, potentially reducing net secretion. The actions of nucleotides alone on Cl<jats:sup>\u2212<\/jats:sup> channel activity of bovine PE cells were studied by electronic cell sorting, patch clamping, and luciferin\/luciferase ATP assay. Cl<jats:sup>\u2212<\/jats:sup>channels were activated by ATP &gt; UTP, ADP, and UDP, but not by 2-methylthio-ATP, all at 100 \u03bcM. UTP triggered ATP release. The second messengers Ca<jats:sup>2+<\/jats:sup>, prostaglandin (PG)E<jats:sub>2<\/jats:sub>, and cAMP activated Cl<jats:sup>\u2212<\/jats:sup> channels without enhancing effects of 100 \u03bcM ATP. Buffering intracellular Ca<jats:sup>2+<\/jats:sup>activity with 1,2-bis(2-aminophenoxy)ethane- N,N,N\u2032,N\u2032- tetraacetic acid or blocking PGE<jats:sub>2<\/jats:sub> formation with indomethacin inhibited ATP-triggered channel activation. The Rp stereoisomer of 8-bromoadenosine 3\u2032,5\u2032-cyclic monophosphothioate inhibited protein kinase A activity but mimicked 8-bromoadenosine 3\u2032,5\u2032-cyclic monophosphate. We conclude that nucleotides can act at &gt;1 P2Y receptor to trigger a sequential cascade involving Ca<jats:sup>2+<\/jats:sup>, PGE<jats:sub>2<\/jats:sub>, and cAMP. cAMP acts directly on Cl<jats:sup>\u2212<\/jats:sup>channels of PE cells, increasing stromal release and potentially reducing net aqueous humor formation and intraocular pressure. <\/jats:p>","DOI":"10.1152\/ajpcell.2001.281.5.c1614","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:35:19Z","timestamp":1514147719000},"page":"C1614-C1623","source":"Crossref","is-referenced-by-count":33,"title":["PGE<sub>2<\/sub>, Ca<sup>2+<\/sup>, and cAMP mediate ATP activation of Cl<sup>\u2212<\/sup> channels in pigmented ciliary epithelial cells"],"prefix":"10.1152","volume":"281","author":[{"given":"Johannes C.","family":"Fleischhauer","sequence":"first","affiliation":[{"name":"Departments of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire H.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Departments of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Peterson-Yantorno","sequence":"additional","affiliation":[{"name":"Departments of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Coca-Prados","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mortimer M.","family":"Civan","sequence":"additional","affiliation":[{"name":"Departments of Physiology and"},{"name":"Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; 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