Abstract
Two major isoforms of angiotensin II receptors, AT1 and AT2, have been defined on the basis of their ligand selectivity. While AT1 is known to mediate typical biological actions of angiotensin II as a cardiovascular regulator, the biological function of AT2 has not yet been established. In the present study using a rat pheochromocytoma cell line, which expresses AT2 exclusively, we found that angiotensin II inhibits phosphotyrosine phosphatase activity in vivo as measured by the inhibition of hydrolysis of [32P]-phosphate from the 32P-labeled synthetic peptide substrate, Raytide. This phosphotyrosine phosphatase inhibition was completely reversed by pertussis toxin, which indicates a G-protein coupled mechanism. In SDS-polyacrylamide gel electrophoresis we found that the phosphotyrosine group of an 85 kDa protein was a substrate mainly preserved, presumably as a consequence of the plausible intracellular phosphotyrosine phosphatase inhibition by angiotensin II.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenal Gland Neoplasms / metabolism*
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Angiotensin II / antagonists & inhibitors
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Angiotensin II / pharmacology*
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Angiotensin Receptor Antagonists
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Animals
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Biphenyl Compounds / pharmacology
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Cell Membrane / metabolism
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Chromatography, Affinity
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Guanosine Diphosphate / analogs & derivatives
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Guanosine Diphosphate / pharmacology
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Imidazoles / pharmacology
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Losartan
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Oligopeptides / pharmacology
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PC12 Cells
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Pertussis Toxin
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Pheochromocytoma / metabolism*
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Phosphates / metabolism
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Phosphoproteins / isolation & purification
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Phosphoproteins / metabolism
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Phosphorus Radioisotopes
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Phosphotyrosine
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Pyridines / pharmacology
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Rats
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Receptors, Angiotensin / physiology*
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Tetrazoles / pharmacology
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Thionucleotides / pharmacology
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Tyrosine / analogs & derivatives
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Tyrosine / analysis
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Virulence Factors, Bordetella / pharmacology
Substances
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Angiotensin Receptor Antagonists
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Biphenyl Compounds
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Imidazoles
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Oligopeptides
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Phosphates
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Phosphoproteins
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Phosphorus Radioisotopes
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Pyridines
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Receptors, Angiotensin
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Tetrazoles
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Thionucleotides
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Virulence Factors, Bordetella
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Angiotensin II
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CGP 42112A
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PD 123319
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Guanosine Diphosphate
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Phosphotyrosine
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Tyrosine
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guanosine 5'-O-(2-thiodiphosphate)
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Pertussis Toxin
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Protein Tyrosine Phosphatases
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Losartan