| First Author | Hiyama TY | Year | 2013 |
| Journal | Cell Metab | Volume | 17 |
| Issue | 4 | Pages | 507-19 |
| PubMed ID | 23541371 | Mgi Jnum | J:299565 |
| Mgi Id | MGI:6501232 | Doi | 10.1016/j.cmet.2013.02.018 |
| Citation | Hiyama TY, et al. (2013) Endothelin-3 expression in the subfornical organ enhances the sensitivity of Na(x), the brain sodium-level sensor, to suppress salt intake. Cell Metab 17(4):507-19 |
| abstractText | Salt homeostasis is essential to survival, but brain mechanisms for salt-intake control have not been fully elucidated. Here, we found that the sensitivity of Na(x) channels to [Na(+)](o) is dose-dependently enhanced by endothelin-3 (ET-3). Na(x) channels began to open when [Na(+)](o) exceeded ~150 mM without ET-3, but opened fully at a physiological [Na(+)](o) (135-145 mM) with 1 nM ET-3. Importantly, ET-3 was expressed in the subfornical organ (SFO) along with Nax, and the level was robustly increased by dehydration. Pharmacological experiments revealed that endothelin receptor B (ET(B)R) signaling is involved in this modulation of Na(x) gating through protein kinase C and ERK1/2 activation. ET(B)R agonists increased the firing rate of GABAergic neurons via lactate in the SFO, and an ET(B)R antagonist attenuated salt aversion during dehydration. These results indicate that ET-3 expression in the SFO is tightly coupled with body-fluid homeostasis through modulation of the [Na(+)](o) sensitivity of Na(x). |
