Endothelin-1 enhances the activity of Na+/Ca2+ exchanger type 1 in renal epithelial cells

J Cardiovasc Pharmacol. 2004 Nov:44 Suppl 1:S239-43. doi: 10.1097/01.fjc.0000166262.19852.b5.

Abstract

The Na+/Ca2+ exchanger, an ion transporter across the plasma membrane, is considered to play a role in calcium reabsorption in the renal nephron. We found that endothelin-1 enhanced Na+/Ca2+ exchange activity in renal epithelial LLC-PK1 cells. Treatment with endothelin-1 increased concomitantly the phosphorylation of Na+/Ca2+ exchanger type 1 (NCX1). Chelerythrine and prolonged exposure to phorbol 12-myristate 13-acetate abolished the activation of NCX1 induced by endothelin-1. To further analyze the activation mechanism of NCX1 by endothelin-1, we examined the effects of endothelin-1 in LLC-PK1 cells expressing NCX1 with mutated exchanger inhibitory peptide regions, which have either no Na+-dependent inactivation (XIP-4YW) or accelerated inactivation (F223E). The exchange activities in LLC-PK1 cells expressing wild-type NCX1 or F223E were stimulated by endothelin-1, but not in cells expressing XIP- 4YW. These results suggest that endothelin-1 activates NCX1 in renal epithelial cells through the pathway of protein kinase C and the process related to Na-dependent inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzophenanthridines / pharmacology
  • Calcium / metabolism
  • Dogs
  • Endothelin-1 / metabolism*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism*
  • LLC-PK1 Cells
  • Mutation
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Sodium / metabolism
  • Sodium-Calcium Exchanger / genetics
  • Sodium-Calcium Exchanger / metabolism*
  • Swine
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection

Substances

  • Benzophenanthridines
  • Endothelin-1
  • Protein Kinase Inhibitors
  • Sodium-Calcium Exchanger
  • sodium-calcium exchanger 1
  • Sodium
  • chelerythrine
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Calcium