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Endothelin‐I induces gene expression through stimulation of endothelin type a receptors in normal rat kidney cells
Author(s) -
Yumet Gladys,
Chin Michael H.,
Carey Brian,
Soprano Kenneth J.,
Lipson Kenneth E.
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041640307
Subject(s) - receptor , microbiology and biotechnology , messenger rna , endothelin 1 , biology , endothelin receptor , stimulation , gene expression , endothelin 3 , medicine , endocrinology , endothelins , gene , biochemistry
RNA blots of total cellular RNA isolated from quiescent and endothelin (ET‐1)‐stimulated normal rat kidney (NRK) cells demonstrated that ET‐1 induced the expression of c‐jun, jun B, and c‐fos mRNA in a time‐dependent manner with maximal expression of mRNA by 1 hr after the addition of ET‐1. Five hundred picomolal ET‐1 was sufficient to induce maximal mRNA expression. These data agreed with saturation experiments which demonstrated that maximal binding of [ 125 I]ET‐1 was achieved at concentrations greater than 100 pM. The K d and B max values for [ 125 I]ET‐1 binding to NRK membranes were 20.5 pM and 22.2 fmol/mg protein, respectively. Competition experiments for the binding of [ 125 I]ET‐1 to NRK membranes demonstrated that ET‐1 was a more potent inhibitor (K i = 0.047 nM) than ET‐3 (K i = 10.8 nM). No specific binding of [ 125 I]ET‐3 (40 or 500 pM) to NRK membranes could be observed. The expression of c‐jun, jun B, and c‐fos mRNA was inhibited by the endothelin type A receptor (ET)‐selective antagonist, BQ‐123. Thus, these data demonstrate that ET‐1 mediates the expression of immediate response gene mRNA in NRK cells via the ET A receptor. ET‐1 stimulation of NRK cells also upregulated EGF receptors, providing a possible mechanism for ET‐1 complementation of epidermal growth factor (EGF) mitogenicity in NRK cells. © 1995 Wiley‐Liss, Inc.