HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 295/4/F1063    most recent 90321.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Bugaj, V. Articles by Stockand, J. D. Search for Related Content PubMed PubMed Citation Articles by Bugaj, V. Articles by Stockand, J. D.

Regulation of the epithelial Na⁺ channel by endothelin-1 in rat collecting duct

¹Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas; and ²Institut National de la Santé et de la Recherche Médicale U773, Centre de Recherche Biomedicale Bichat-Beaujon and Universite Paris, Paris, France

Submitted 19 May 2008 ; accepted in final form 24 July 2008

We used patch-clamp electrophysiology to investigate regulation of the epithelial Na⁺ channel (ENaC) by endothelin-1 (ET-1) in isolated, split-open rat collecting ducts. ET-1 significantly decreases ENaC open probability by about threefold within 5 min. ET-1 decreases ENaC activity through basolateral membrane ET_B but not ET_A receptors. In rat collecting duct, we find no role for phospholipase C or protein kinase C in the rapid response of ENaC to ET-1. ET-1, although, does activate src family tyrosine kinases and their downstream MAPK1/2 effector cascade in renal principal cells. Both src kinases and MAPK1/2 signaling are necessary for ET-1-dependent decreases in ENaC open probability in the split-open collecting duct. We conclude that ET-1 in a physiologically relevant manner rapidly suppresses ENaC activity in native, mammalian principal cells. These findings may provide a potential mechanism for the natriuresis observed in vivo in response to ET-1, as well as a potential cause for the salt-sensitive hypertension found in animals with impaired endothelin signaling.

salt-sensitive hypertension; systemic blood pressure

This article has been cited by other articles:

				V. Bugaj, O. Pochynyuk, and J. D. Stockand Activation of the epithelial Na+ channel in the collecting duct by vasopressin contributes to water reabsorption Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1411 - F1418. [Abstract] [Full Text] [PDF]

				L. R. Stow, M. L. Gumz, I. J. Lynch, M. M. Greenlee, A. Rudin, B. D. Cain, and C. S. Wingo Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1) J. Biol. Chem., October 30, 2009; 284(44): 30087 - 30096. [Abstract] [Full Text] [PDF]