Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 microA/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 microM) 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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PMID:Epidermal growth factor inhibits amiloride-sensitive sodium absorption in renal collecting duct cells. 1238 7

Bone morphogenetic protein (BMP)-7 exerts dose-dependent stimulatory and inhibitory effects during renal branching morphogenesis. Previously, we identified an inhibitory role for activin-like kinase receptors and Smad1 in BMP-dependent inhibition (Piscione, T. D., Phan, T., and Rosenblum, N. D. (2001) Am. J. Physiol. 280, F19-F33). Here we demonstrate a novel role for p38 mitogen-activated kinase (p38(MAPK)) in BMP7-dependent stimulatory signaling. Stimulatory doses (0.25 nm) of BMP7 increased p38(MAPK) activity and stimulated phosphorylation of endogenous activating transcription factor 2 (ATF2) in a p38(MAPK)-dependent manner in murine inner medullary collecting duct (mIMCD-3) cells. In contrast, high doses (10 nm) of BMP7 inhibited p38(MAPK) activity and phosphorylation of endogenous ATF2. Treatment with BMP7 exerted no significant effect on the levels of the phosphorylated forms of endogenous SAPK/JNK or p44 and p42 (ERK1 and ERK2) protein kinases. To investigate the functional importance of p38(MAPK) signaling, we showed that SB203580, a p38(MAPK) inhibitor, blocked the stimulatory effect of BMP7 on mIMCD-3 cell morphogenesis but had no effect on BMP7-dependent inhibition in a three-dimensional culture model. To identify mechanisms by which BMP7-dependent inhibitory signaling suppresses p38(MAPK) activity, we measured p38(MAPK) activity in ligand independent mIMCD-3 models of enhanced and suppressed Smad signaling. Basal activity of p38(MAPK) was decreased in mIMCD-3 cells and in embryonic kidney tissue expressing a constitutively active activin-like kinase receptor, but was increased in mIMCD-3 cells stably expressing a dominant negative form of Smad1. We conclude that BMP7 stimulates renal epithelial cell morphogenesis via p38(MAPK) and that p38(MAPK) activity is negatively regulated by Smad1.
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PMID:p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1. 1471 43

Receptor-mediated inhibition of amiloride-sensitive sodium absorption was observed in primary and immortalized murine renal collecting duct cell (mCT12) monolayers. The addition of epidermal growth factor (EGF) to the basolateral bathing solution of polarized monolayers reduced amiloride-sensitive short-circuit current (I(sc)) by 15-25%, whereas the addition of ATP to the apical bathing solution decreased I(sc) by 40-60%. Direct activation of PKC with phorbol 12-myristate 13-acetate (PMA) and mobilization of intracellular calcium with 2,5-di-tert-butyl-hydroquinone (DBHQ) reduced amiloride-sensitive I(sc) in mCT12 monolayers by 46 +/- 4% (n = 8) and 22 +/- 2% (n = 8), respectively. Exposure of mCT12 cells to EGF, ATP, PMA, and DBHQ caused an increase in phosphorylation of p42/p44 (extracellular signal-regulated kinase; ERK1/2). Pretreatment of mCT12 monolayers with an ERK kinase inhibitor (PD-98059; 30 microM) prevented phosphorylation of p42/p44 and significantly reduced EGF, ATP, and PMA-induced inhibition of amiloride-sensitive I(sc). In contrast, pretreatment of monolayers with a PKC inhibitor (bisindolylmaleimide I; GF109203x; 1 microM) almost completely blocked the PMA-induced decrease in I(sc), but did not alter the EGF- or ATP-induced inhibition of I(sc). The DBHQ-mediated decrease in I(sc) was due to inhibition of basolateral Na(+)-K(+)-ATPase, but EGF-, ATP-, and PMA-induced inhibition was most likely due to reduced apical sodium entry (epithelial Na(+) channel activity). The results of these studies demonstrate that acute inhibition of amiloride-sensitive sodium transport by extracelluar ATP and EGF involves ERK1/2 activation and suggests a role for MAP kinase signaling as a negative regulator of electrogenic sodium absorption in epithelia.
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PMID:A role for ERK1/2 in EGF- and ATP-dependent regulation of amiloride-sensitive sodium absorption. 1563 42