{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T02:09:48Z","timestamp":1773281388873,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,11,22]],"date-time":"2013-11-22T00:00:00Z","timestamp":1385078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The nitric oxide (NO) donor sodium nitroprusside (SNP) is known to reduce aqueous humor (AH) secretion in the isolated porcine eye. Previously, SNP was found to inhibit Na,K\u2010ATPase activity in nonpigmented ciliary epithelium (NPE), AH\u2010secreting cells, through a cGMP\/protein kinase G (PKG)\u2010mediated pathway. Here we show Src family kinase (SFK) activation in the Na,K\u2010ATPase activity response to SNP. Ouabain\u2010sensitive <jats:sup>86<\/jats:sup>Rb uptake was reduced by &gt;35% in cultured NPE cells exposed to SNP (100\u2009\u00b5M) or exogenously added cGMP (8\u2010Br\u2010cGMP) (100\u2009\u00b5M) and the SFK inhibitor PP2 (10\u2009\u00b5M) prevented the response. Ouabain\u2010sensitive ATP hydrolysis was reduced by \u223c40% in samples detected in material obtained from SNP\u2010 and 8\u2010Br\u2010cGMP\u2010treated cells following homogenization, pointing to an intrinsic change of Na,K\u2010ATPase activity. Tyrosine\u201010 phosphorylation of Na,K\u2010ATPase \u03b11 subunit was detected in SNP and <jats:sc>L<\/jats:sc>\u2010arginine\u2010treated cells and the response prevented by PP2. SNP elicited an increase in cell cGMP. Cells exposed to 8\u2010Br\u2010cGMP displayed SFK activation (phosphorylation) and inhibition of both ouabain\u2010sensitive <jats:sup>86<\/jats:sup>Rb uptake and Na,K\u2010ATPase activity that was prevented by PP2. SFK activation, which also occurred in SNP\u2010treated cells, was suppressed by inhibitors of soluble guanylate cyclase (ODQ; 10\u2009\u00b5M) and PKG (KT5823; 1\u2009\u00b5M). SNP and 8\u2010Br\u2010cGMP also increased phosphorylation of ERK1\/2 and p38 MAPK and the response prevented by PP2. However, U0126 did not prevent SNP or 8\u2010Br\u2010cGMP\u2010induced inhibition of Na,K\u2010ATPase activity. Taken together, the results suggest that NO activates guanylate cyclase to cause a rise in cGMP and subsequent PKG\u2010dependent SFK activation. Inhibition of Na,K\u2010ATPase activity depends on SFK activation. J. Cell. Physiol. 229: 343\u2013352, 2014. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.24454","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T12:58:37Z","timestamp":1377176317000},"page":"343-352","source":"Crossref","is-referenced-by-count":17,"title":["Nitric Oxide Regulation of Na, K\u2010ATPase Activity in Ocular Ciliary Epithelium Involves Src Family Kinase"],"prefix":"10.1002","volume":"229","author":[{"given":"Mohammad","family":"Shahidullah","sequence":"first","affiliation":[{"name":"Department of Physiology University of Arizona Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amritlal","family":"Mandal","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Arizona Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guojun","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Arizona Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas A.","family":"Delamere","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Arizona Tucson Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402152200"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(87)90142-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1076\/0271-3683(200006)2061-YFT511","article-title":"The effect of L\u2010arginine on intraocular pressure in the human eye","volume":"20","author":"Chuman H","year":"2000","journal-title":"Curr Eye Res"},{"key":"e_1_2_6_5_1","first-page":"1","volume-title":"Transport components of net secretion of the aqueous humour and their integrated regulation. The Eye's Aqueous Humor: From secretion to glaucoma","author":"Civan MM","year":"1998"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2003.09.021"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms130910697"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00928-5"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.6.C1685"},{"key":"e_1_2_6_10_1","first-page":"2625","article-title":"Carbachol and nitric oxide inhibition of Na,K\u2010ATPase activity in bovine ciliary processes","volume":"42","author":"Ellis DZ","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2750"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-5072"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(87)90493-6"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp021844"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.9.2847"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V25976"},{"key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1016\/S0021-9258(19)39891-6","article-title":"Cellular distribution and differential gene expression of the three alpha subunit isoforms of the Na,K\u2010ATPase in the ocular ciliary epithelium","volume":"265","author":"Ghosh S","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.15.6391-6403.2005"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117895"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311715200"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00516.2007"},{"key":"e_1_2_6_22_1","first-page":"181","article-title":"Effect of a nitric oxide donor on intraocular pressure","volume":"100","author":"Kojima S","year":"1996","journal-title":"Nippon Ganka Gakkai Zasshi\u2010 Acta Societatis Ophthalmologicae Japonicae"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026342"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22602"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/108076801750295263"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04083.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00233-6"},{"key":"e_1_2_6_28_1","first-page":"1460","article-title":"Genistein inhibits the regulation of active sodium\u2010potassium transport by dopaminergic agonists in nonpigmented ciliary epithelium","volume":"40","author":"Nakai Y","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.24.2.114.8162"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00334.2001"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2001423"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.171"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-005-5616-1"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706795"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0397"},{"key":"e_1_2_6_36_1","first-page":"1","article-title":"cGMP, sodiun nitroprusside and sodium azide reduce aqueous humour formation in the isolated arterially perfused pig eye","volume":"144","author":"Shahidullah M","year":"2005","journal-title":"Br J Pharmacol"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713680701434899"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22858"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.1998.00312.x"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/792639"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00579.2006"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.13.1.513"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.08.002"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(89)90470-3"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00882.2003"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.24454","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.24454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T16:45:15Z","timestamp":1696351515000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.24454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,22]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1002\/jcp.24454"],"URL":"https:\/\/doi.org\/10.1002\/jcp.24454","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,22]]}}}