Effect of adenosine triphosphate on phosphate uptake in renal proximal tubule cells: Involvement of PKC and p38 MAPK

✍ Scribed by Yun Jung Lee; Soo Hyun Park; Tae Oh Jeung; Kee Won Kim; Jang Hern Lee; Ho Jae Han

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 355 KB
• Volume: 205
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20367

✦ Synopsis

Abstract

ATP has been known to act as an extracellular signal and to be involved in various functions of kidney. Renal proximal tubular reabsorption of phosphate (P~i~) contributes to the maintenance of phosphate homeostasis, which is regulated by Na^+^/P~i~ cotransporter. However, the effects of ATP on Na^+^/P~i~ cotransporters were not elucidated in proximal tubule cells (PTCs). Thus, the effects of ATP on Na^+^/P~i~ cotransporter and its related signal pathways are examined in the primary cultured renal PTCs. In the present study, ATP inhibited P~i~ uptake in a time (> 1 h) and dose (>10^−6^M) dependent manner. ATP‐induced inhibition of P~i~ uptake was correlated with the decrease of type II Na^+^/P~i~ cotransporter mRNA. ATP‐induced inhibition of P~i~ uptake may be mediated by P2Y receptor activation, since suramin (non‐specific P2 receptor antagonist) and RB‐2 (P2Y receptor antagonist) blocked it. ATP‐induced inhibition of P~i~ uptake was blocked by neomycin, U73122 (phospholipase C (PLC) inhibitors), bisindolylmaleimide I, H‐7, and staurosporine (protein kinase C (PKC) inhibitors), suggesting the role of PLC/PKC pathway. ATP also increased inositol phosphates (IPs) formation and induced PKC translocation from cytosolic fraction to membrane fraction. In addition, ATP‐induced inhibition of P~i~ uptake was blocked by SB 203580 [a p38 mitogen activated protein kinase (MAPK) inhibitor], but not by PD 98059 (a p44/42 MAPK inhibitor). Indeed, ATP induced phosphorylation of p38 MAPK, which was not blocked by PKC inhibitor. In conclusion, ATP inhibited P~i~ uptake via PLC/PKC as well as p38 MAPK in renal PTCs. © 2005 Wiley‐Liss, Inc.