| First Author | Coble JP | Year | 2014 |
| Journal | Hypertension | Volume | 64 |
| Issue | 1 | Pages | 141-8 |
| PubMed ID | 24777977 | Mgi Jnum | J:248601 |
| Mgi Id | MGI:6094181 | Doi | 10.1161/HYPERTENSIONAHA.114.03461 |
| Citation | Coble JP, et al. (2014) Activity of protein kinase C-alpha within the subfornical organ is necessary for fluid intake in response to brain angiotensin. Hypertension 64(1):141-8 |
| abstractText | 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 V(1)A and V(2) receptors, corrected the elevated water intake of sRA mice. Using an isoform selective inhibitor and an adenovirus expressing dominant negative protein kinase C-alpha revealed that protein kinase C-alpha 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-alpha 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-alpha signaling in the subfornical organ in fluid intake stimulated by angiotensin-II in the brain. |
