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Effect of adenosine triphosphate on phosphate uptake in renal proximal tubule cells: Involvement of PKC and p38 MAPK
Author(s) -
Lee Yun Jung,
Park Soo Hyun,
Jeung Tae Oh,
Kim Kee Won,
Lee Jang Hern,
Han Ho Jae
Publication year - 2005
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.20367
Subject(s) - protein kinase c , reabsorption , cotransporter , adenosine triphosphate , phospholipase c , bisindolylmaleimide , adenosine , chemistry , mapk/erk pathway , p2y receptor , protein kinase a , kinase , biology , microbiology and biotechnology , medicine , signal transduction , endocrinology , biochemistry , kidney , purinergic receptor , sodium , organic chemistry
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.