{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:56:36Z","timestamp":1785466596425,"version":"3.56.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:p>\n            Angiotensin-II production in the subfornical organ acting through angiotensin-II type-1 receptors is necessary for polydipsia, resulting from elevated renin\u2013angiotensin system activity. Protein kinase C and mitogen-activated protein kinase pathways have been shown to mediate effects of angiotensin-II in the brain. We investigated mechanisms that mediate brain angiotensin-II\u2013induced polydipsia. We used double-transgenic sRA mice, consisting of human renin controlled by the neuron-specific synapsin promoter crossed with human angiotensinogen controlled by its endogenous promoter, which results in brain-specific overexpression of angiotensin-II, particularly in the subfornical organ. We also used the deoxycorticosterone acetate-salt model of hypertension, which exhibits polydipsia. Inhibition of protein kinase C, but not extracellular signal\u2013regulated kinases, protein kinase A, or vasopressin V\n            <jats:sub>1A<\/jats:sub>\n            and V\n            <jats:sub>2<\/jats:sub>\n            receptors, corrected the elevated water intake of sRA mice. Using an isoform selective inhibitor and an adenovirus expressing dominant negative protein kinase C-\u03b1 revealed that protein kinase C-\u03b1 in the subfornical organ was necessary to mediate elevated fluid and sodium intake in sRA mice. Inhibition of protein kinase C activity also attenuated polydipsia in the deoxycorticosterone acetate-salt model. We provide evidence that inducing protein kinase C activity centrally is sufficient to induce water intake in water-replete wild-type mice, and that cell surface localization of protein kinase C-\u03b1 can be induced in cultured cells from the subfornical organ. These experimental findings demonstrate a role for central protein kinase C activity in fluid balance, and further mechanistically demonstrate the importance of protein kinase C-\u03b1 signaling in the subfornical organ in fluid intake stimulated by angiotensin-II in the brain.\n          <\/jats:p>","DOI":"10.1161\/hypertensionaha.114.03461","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T03:10:35Z","timestamp":1398741035000},"page":"141-148","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Activity of Protein Kinase C-\u03b1 Within the Subfornical Organ Is Necessary for Fluid Intake in Response to Brain Angiotensin"],"prefix":"10.1161","volume":"64","author":[{"given":"Jeffrey P.","family":"Coble","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (J.P.C., J.L.G., C.D.S.), Psychology (R.F.J., A.K.J.), and Anatomy and Cell Biology (M.D.C.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph F.","family":"Johnson","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (J.P.C., J.L.G., C.D.S.), Psychology (R.F.J., A.K.J.), and Anatomy and Cell Biology (M.D.C.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin D.","family":"Cassell","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (J.P.C., J.L.G., C.D.S.), Psychology (R.F.J., A.K.J.), and Anatomy and Cell Biology (M.D.C.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan Kim","family":"Johnson","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (J.P.C., J.L.G., C.D.S.), Psychology (R.F.J., A.K.J.), and Anatomy and Cell Biology (M.D.C.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin L.","family":"Grobe","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (J.P.C., J.L.G., C.D.S.), Psychology (R.F.J., A.K.J.), and Anatomy and Cell Biology (M.D.C.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curt D.","family":"Sigmund","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (J.P.C., J.L.G., C.D.S.), Psychology (R.F.J., A.K.J.), and Anatomy and Cell Biology (M.D.C.), Roy J. and Lucille A. 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