The role of the phosphoinositide pathway in hormonal regulation of the epithelial sodium channel

Advances in Experimental Medicine and Biology
B L Blazer-Yost, Charity Nofziger

Abstract

In summary, insulin and aldosterone stimulate phosphatidylinositol phosphorylation, thus indicating the existence of a regulated protein at or before the PI3-kinase step. Aldosterone induces the synthesis of sgk, a downstream element of the PI pathway. Sgk is necessary, but not rate-limiting, for aldosterone- and insulin-stimulated Na+ transport. However, the enzyme appears to be rate-limiting for the natriferic action of ADH. Insulin-stimulated Na+ transport, an acute response, is dependent on PI3-kinase activity but the magnitude of the response is not altered by a cellular excess of sgk. ADH-stimulated transport is not dependent on PI3-kinase but is potentiated by an excess of sgk. The foregoing data indicate that the PI pathway is involved in several steps of the natriferic action of hormones and intersects with other pathways which regulate ENaC. Furthermore, the data are consistent with the hypothesis that activation of PI3-kinase may ultimately stimulate channel insertion as well as regulate channel endocytosis. Both of these phenomena can result in an increase of ENaC-mediated Na+ transport.

Citations

Apr 30, 2009·The Journal of Biological Chemistry·Thomas R KleymanRebecca P Hughey
May 13, 2010·The Journal of Biological Chemistry·James K Bubien
Dec 29, 2013·American Journal of Physiology. Cell Physiology·Qian Wang, Bruce D Schultz
Oct 5, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Michael W Brands, M Marlina Manhiani
Jul 29, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Markus ReschDierk H Endemann
Jan 14, 2011·American Journal of Physiology. Renal Physiology·M Marlina ManhianiMichael W Brands

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