Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9894452 | Regulatory Peptides | 2005 | 7 Pages |
Abstract
Angiotensin II (Ang II) increases the cytosolic Ca2+ concentration in different cell types. In this study, we investigate the effect of Ang II on the Ca2+ ATPase of purified basolateral membranes of kidney proximal tubules. This enzyme pumps Ca2+ out of the cytosol in a reaction coupled to ATP hydrolysis, and it is responsible for the fine-tuned regulation of cytosolic Ca2+ activity. Ca2+-ATPase activity is inhibited by picomolar concentrations of Ang II, with maximal inhibition being attained at â50% of the control values. The presence of raising concentrations (10â11 to 10â7 M) of losartan (an AT1-receptor antagonist) or PD123319 (an AT2-receptor antagonist) gradually reverts inhibition by Ang II. Both the phospholipase C (PLC) inhibitor U-73122 (10â6 M) and the inhibitor of protein kinase C (PKC) staurosporine (10â7 M) prevent inhibition of the Ca2+ pump by Ang II. Incubation of the previously isolated membranes with a PKC activator-the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (10â8 M)-mimics the inhibition found with Ang II, and the effects of the compounds are not additive. Taken as a whole, these results indicate the Ang II inhibits Ca2+-ATPase by activation of a PKC system present in primed state in these membranes after binding of the hormone to losartan- and PD123319-sensitive receptors coupled to a PLC. Therefore, inhibition of the basolateral membrane Ca2+-ATPase by kinase-mediated phosphorylation appears to be one of the pathways by which Ang II promotes an increase in the cytosolic Ca2+ concentration of proximal tubule cells.
Keywords
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Iranaia Assunção-Miranda, Adilson L. Guilherme, Clédson Reis-Silva, Glória Costa-Sarmento, Mécia M. Oliveira, Adalberto Vieyra,