Long-term regulation of vacuolar H(+)-ATPase by angiotensin II in proximal tubule cells.
Long-term effects of angiotensin II (Ang II) on vacuolar H(+)-ATPase were studied in a SV40-transformed cell line derived from rat proximal tubules (IRPTC). Using pH(i) measurements with the fluorescent dye BCECF, the hormone increased Na(+)-independent pH recovery rate from an NH(4)Cl pulse from 0.066 +/- 0.014 pH U/min (n = 7) to 0.14 +/- 0.021 pH U/min (n = 13; p < 0.05) in 10 h Ang II (10(-9) M)-treated cells. The increased activity of H(+)-ATPase did not involve changes in mRNA or protein abundance of the B2 subunit but increased cell surface expression of the V-ATPase. Inhibition of tyrosine kinase by genistein blocked Ang II-dependent stimulation of H(+)-ATPase. Inhibition of phosphatidylinositol-3-kinase (PI3K) by wortmannin and of p38 mitogen-activated protein kinase (MAPK) by SB 203580 also blocked this effect. Thus, long-term exposure of IRPTC cells to Ang II causes upregulation of H(+)-ATPase activity due, at least in part, to increased B2 cell surface expression. This regulatory pathway is dependent on mechanisms involving tyrosine kinase, p38 MAPK, and PI3K activation.
Carraro-Lacroix
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LR
Institute of Biomedical Sciences, Physiology and Biophysics Department, University of São Paulo, Av. Professor Lineu Prestes, 1524, Sala 231, Cidade Universitária, São Paulo, SP, CEP 05508-900, Brazil.
Girardi
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AC
Malnic
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D000643:Ammonium Chloride / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002021:Buffers; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D019808:Losartan / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000643:Ammonium Chloride; D000730:Androstadienes; D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D002021:Buffers; D003513:Cycloheximide; D003609:Dactinomycin; D019833:Genistein; D007093:Imidazoles; D019808:Losartan; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D011505:Protein-Tyrosine Kinases; D011725:Pyridines; D025262:Vacuolar Proton-Translocating ATPases; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580