Endothelin-1 enhances the activity of Na+/Ca2+ exchanger type 1 in renal epithelial cells.
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.
Kita
Satomi
S
Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Katsuragi
Takeshi
T
Iwamoto
Takahiro
T
D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D019332:Endothelin-1 / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018374:LLC-PK1 Cells; D009154:Mutation; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D053119:Benzophenanthridines; D019332:Endothelin-1; D047428:Protein Kinase Inhibitors; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D012964:Sodium; C016299:chelerythrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium