Endothelin-3 expression in the subfornical organ enhances the sensitivity of Nax, the brain sodium-level sensor, to suppress salt intake

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 (ET BR) 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.

Original languageEnglish
Pages (from-to)507-519
Number of pages13
JournalCell Metabolism
Volume17
Issue number4
DOIs
Publication statusPublished - Apr 2 2013
Externally publishedYes

Fingerprint

Subfornical Organ
Endothelin-3
Salts
Sodium
Brain
Dehydration
Homeostasis
Endothelin B Receptors
GABAergic Neurons
Body Fluids
Protein Kinase C
Lactic Acid
Pharmacology

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Endothelin-3 expression in the subfornical organ enhances the sensitivity of Nax, the brain sodium-level sensor, to suppress salt intake. / Hiyama, Takeshi Y.; Yoshida, Masahide; Matsumoto, Masahito; Suzuki, Ryoko; Matsuda, Takashi; Watanabe, Eiji; Noda, Masaharu.

In: Cell Metabolism, Vol. 17, No. 4, 02.04.2013, p. 507-519.

Research output: Contribution to journalArticle

Hiyama, Takeshi Y. ; Yoshida, Masahide ; Matsumoto, Masahito ; Suzuki, Ryoko ; Matsuda, Takashi ; Watanabe, Eiji ; Noda, Masaharu. / Endothelin-3 expression in the subfornical organ enhances the sensitivity of Nax, the brain sodium-level sensor, to suppress salt intake. In: Cell Metabolism. 2013 ; Vol. 17, No. 4. pp. 507-519.
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