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Atrial natriuretic peptide-stimulated Ca 2+ reabsorption in rabbit kidney requires membrane-targeted, cGMP-dependent protein kinase type II

1999; National Academy of Sciences; Volume: 96; Issue: 11 Linguagem: Inglês

10.1073/pnas.96.11.6084

1091-6490

Joost G.J. Hoenderop, Arie B. Vaandrager, Lisette Dijkink, Albert Smolenski, Stepan Gambaryan, Suzanne M. Lohmann, Hugo R. de Jonge, Peter H.G.M. Willems, René J.M. Bindels,

Heart Failure Treatment and Management

Atrial natriuretic peptide (ANP) and nitric oxide (NO) are key regulators of ion and water transport in the kidney. Here, we report that these cGMP-elevating hormones stimulate Ca 2+ reabsorption via a novel mechanism specifically involving type II cGMP-dependent protein kinase (cGK II). ANP and the NO donor, sodium nitroprusside (SNP), markedly increased Ca 2+ uptake in freshly immunodissected rabbit connecting tubules (CNT) and cortical collecting ducts (CCD). Although readily increasing cGMP, ANP and SNP did not affect Ca 2+ and Na + reabsorption in primary cultures of these segments. Immunoblot analysis demonstrated that cGK II, and not cGK I, was present in freshly isolated CNT and CCD but underwent a complete down-regulation during the primary cell culture. However, upon adenoviral reexpression of cGK II in primary cultures, ANP, SNP, and 8-Br-cGMP readily increased Ca 2+ reabsorption. In contrast, no cGMP-dependent effect on electrogenic Na + transport was observed. The membrane localization of cGK II proved to be crucial for its action, because a nonmyristoylated cGK II mutant that was shown to be localized in the cytosol failed to mediate ANP-stimulated Ca 2+ transport. The Ca 2+ -regulatory function of cGK II appeared isotype-specific because no cGMP-mediated increase in Ca 2+ transport was observed after expression of the cytosolic cGK Iβ or a membrane-bound cGK II/Iβ chimer. These results demonstrate that ANP- and NO-stimulated Ca 2+ reabsorption requires membrane-targeted cGK II.