Hormonal-dependent recruitment of Na+,K+-ATPase to the plasmalemma is mediated by PKC beta and modulated by [Na+]i.
Autor: | Budu, Claudia E, Efendiev, Riad, Cinelli, Angel M, Bertorello, Alejandro M, Pedemonte, Carlos H |
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Předmět: |
SODIUM metabolism
ADENOSINE triphosphatase ANIMAL experimentation CELL membranes CELL receptors COMPARATIVE studies CYTOSOL DOSE-effect relationship in pharmacology ENZYME inhibitors KIDNEYS MAMMALS RESEARCH methodology MEDICAL cooperation PROTEIN kinases RESEARCH SODIUM TRANSFERASES EVALUATION research CHEMICAL inhibitors PHARMACODYNAMICS |
Zdroj: | British Journal of Pharmacology; Dec2002, Vol. 137 Issue 8, p1380-1386, 7p |
Abstrakt: | 1. The present study demonstrates that stimulation of hormonal receptors of proximal tubule cells with the serotonin-agonist 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) induces an augmentation of Na(+),K(+)-ATPase activity that results from the recruitment of enzyme molecules to the plasmalemma. 2. Cells expressing the rodent wild-type Na(+),K(+)-ATPase alpha-subunit had the same basal Na(+),K(+)-ATPase activity as cells expressing the alpha-subunit S11A or S18A mutants, but stimulation of Na(+),K(+)-ATPase activity was completely abolished in either mutant. 3. 8-OH-DPAT treatment of OK cells led to PKC(beta)-dependent phosphorylation of the alpha-subunit Ser-11 and Ser-18 residues, and determination of enzyme activity with the S11A and S18A mutants indicated that both residues are essential for the agonist-dependent stimulation of Na(+),K(+)-ATPase activity. 4. When cells were treated with both dopamine and 8-OH-DPAT, an activation of Na(+),K(+)-ATPase was observed at basal intracellular sodium concentration (approximately 9 mM), and this activation was gradually reduced and became a significant inhibition as the concentration of intracellular sodium gradually increased from 9 to 19 mM. Thus, besides the antagonistic effects of dopamine and 8-OH-DPAT, intracellular sodium modulates whether an activation or an inhibition of Na(+),K(+)-ATPase is produced. [ABSTRACT FROM AUTHOR] |
Databáze: | Complementary Index |
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