Activity of protein kinase C-α within the subfornical organ is necessary for fluid intake in response to brain angiotensin

Jeffrey P Coble; Ralph F Johnson; Martin D Cassell; Alan Kim Johnson; Justin L Grobe; Curt D Sigmund

doi:10.1161/HYPERTENSIONAHA.114.03461

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Activity of protein kinase C-α within the subfornical organ is necessary for fluid intake in response to brain angiotensin

Journal article

Open access

Peer reviewed

Activity of protein kinase C-α within the subfornical organ is necessary for fluid intake in response to brain angiotensin

Jeffrey P Coble, Ralph F Johnson, Martin D Cassell, Alan Kim Johnson, Justin L Grobe and Curt D Sigmund

Hypertension (Dallas, Tex. 1979), Vol.64(1), pp.141-148

07/2014

DOI: 10.1161/HYPERTENSIONAHA.114.03461

PMCID: PMC4057298

PMID: 24777977

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Abstract

Angiotensin-II production in the subfornical organ acting through angiotensin-II type-1 receptors is necessary for polydipsia, resulting from elevated renin-angiotensin 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-induced 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-regulated kinases, protein kinase A, or vasopressin V₁A and V₂ receptors, corrected the elevated water intake of sRA mice. Using an isoform selective inhibitor and an adenovirus expressing dominant negative protein kinase C-α revealed that protein kinase C-α 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-α 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-α signaling in the subfornical organ in fluid intake stimulated by angiotensin-II in the brain.

Protein Kinase C-alpha - antagonists & inhibitors

Protein Kinase C-alpha - metabolism

Drinking - physiology

Male

Mice, Transgenic

Renin-Angiotensin System - physiology

Hypertension - metabolism

Subfornical Organ - drug effects

Brain - drug effects

Brain - metabolism

Animals

Female

Renin-Angiotensin System - drug effects

Mice

Subfornical Organ - metabolism

Details

Title: Subtitle: Activity of protein kinase C-α within the subfornical organ is necessary for fluid intake in response to brain angiotensin
Creators: Jeffrey P Coble - 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
Ralph F Johnson - 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
Martin D Cassell - 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
Alan Kim Johnson - 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
Justin L Grobe - 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
Curt D Sigmund - 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. curt-sigmund@uiowa.edu
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.64(1), pp.141-148
DOI: 10.1161/HYPERTENSIONAHA.114.03461
PMID: 24777977
PMCID: PMC4057298
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Publisher: United States
Grant note: HL014388 / NHLBI NIH HHS HL084207 / NHLBI NIH HHS R01 HL098207 / NHLBI NIH HHS R01 HL061446 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS P01 HL062984 / NHLBI NIH HHS MH08024 / NIMH NIH HHS R37 HL048058 / NHLBI NIH HHS K99 HL098276 / NHLBI NIH HHS HL048058 / NHLBI NIH HHS R00 HL098276 / NHLBI NIH HHS R01 MH080241 / NIMH NIH HHS HL061446 / NHLBI NIH HHS HL098207 / NHLBI NIH HHS P01 HL014388 / NHLBI NIH HHS HL098276 / NHLBI NIH HHS R01 HL048058 / NHLBI NIH HHS P01 HL084207 / NHLBI NIH HHS HL062984 / NHLBI NIH HHS
Language: English
Date published: 07/2014
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Psychological and Brain Sciences; Neuroscience and Pharmacology; Health, Sport, and Human Physiology
Record Identifier: 9984002442502771

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