期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 284, 期 1, 页码 F57-F64出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00028.2002
关键词
extracellular signal-regulated protein kinase; ERK1/2; polycystic kidney disease; mitogen-activated protein kinase
资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK027651, P50DK057306] Funding Source: NIH RePORTER
- NIDDK NIH HHS [P30-DK-27651, P50-DK-57306] Funding Source: Medline
The effects of the ERK pathway on electrogenic transepithelial Na+ absorption by renal collecting duct cells were determined. Approximately 90% of the unstimulated short-circuit current (15 +/- 1 muA/cm(2), n = 10) across conditionally immortalized murine collecting duct epithelial cells (mCT1) is amiloride sensitive and is likely mediated by apical epithelial Na+ channels. Chronic exposure (24 h) of the epithelial monolayers to either EGF (50 ng/ml) or transforming growth factor-alpha (TGF-alpha; 20 ng/ml) reduced amiloride-sensitive short-circuit current by >60%. The inhibitory effect of EGF on Na+ absorption was not due to inhibition of basolateral Na+-K+-ATPase, because the pump current elicited by permeabilization of apical membrane with nystatin was not reduced by EGF. Chronic exposure of the mCT1 cells to EGF (20 ng/ml, 24 h) elicited a 70-85% decrease in epithelial Na+ channel subunit mRNA levels. Exposure of mCT1 cells to either EGF (20 ng/ml) or PMA (150 nM) induced rapid phosphorylation of p42/p44 (ERK1/2) and pretreatment of the monolayers with PD-98059 (an ERK kinase inhibitor; 30 muM) prevented phosphorylation of p42/p44. Similarly, pretreatment of mCT1 monolayers with PD-98059 prevented the EGF- and PMA-induced inhibition of amiloride-sensitive Na+ absorption. The results of these studies demonstrate that amiloride-sensitive Na+ absorption by renal collecting duct cells is regulated by the ERK pathway. This pathway may play a role in alterations in ion transport that occur in polycystic kidney disease.
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