Endothelin-I induces gene expression through stimulation of endothelin type a receptors in normal rat kidney cells
✍ Scribed by Gladys Yumet; Michael H. Chin; Brian Carey; Kenneth J. Soprano; Kenneth E. Lipson
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 840 KB
- Volume
- 164
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
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 picomolar ET-1 was sufficient to induce maximal mRNA expression. These data agreed with saturation experiments which demonstrated that maximal binding of ['251]ET-1 was achieved at concentrations greater than 100 pM. The K, and B , , , , values for ['L51]ET-l binding to NRK membranes were 20.5 pM and 22.2 fmolimg protein, respectively. Competition experiments for the binding of ['-?'I]ET-1 to NRK membranes demonstrated that ET-1 was a more potent inhibitor (K, = 0.047 nM) than ET-3 (K, = 10.8 nM). No specific binding of ['251]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 ETA 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.