Details

Autor(en) / Beteiligte

• Hiyama, Takeshi Y.
• Yoshida, Masahide
• Matsumoto, Masahito
• Suzuki, Ryoko
• Matsuda, Takashi
• Watanabe, Eiji
• Noda, Masaharu

Titel

Endothelin-3 Expression in the Subfornical Organ Enhances the Sensitivity of Nax, the Brain Sodium-Level Sensor, to Suppress Salt Intake

Ist Teil von

• Cell metabolism, 2013-04, Vol.17 (4), p.507-519

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2013

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 Nax channels to [Na+]o is dose-dependently enhanced by endothelin-3 (ET-3). Nax 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 (ETBR) signaling is involved in this modulation of Nax gating through protein kinase C and ERK1/2 activation. ETBR agonists increased the firing rate of GABAergic neurons via lactate in the SFO, and an ETBR 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 Nax. ► Expression level of ET-3 is robustly upregulated in the SFO by dehydration ► Sensitivity of Nax channels to [Na+]o is dose-dependently enhanced by ET-3 ► The sodium-level sensor sensitivity is enhanced through activation of ETBR ► An ETBR antagonist attenuated Nax-dependent salt aversion during dehydration