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ATP-independent activation of natriuretic peptide receptors

Natriuretic peptide receptor A (NPR-A) is an essential cardiovascular regulator that is stimulated by atrial natriuretic peptide and brain natriuretic peptide, whereas natriuretic peptide receptor B (NPR-B) stimulates long bone growth in a C-type natriuretic peptide-dependent manner. Many reports indicate that ATP is essential for NPR-A and NPR-B activation. Current models suggest that natriuretic peptide binding to receptor extracellular domains causes ATP binding to intracellular kinase homology domains, which derepresses adjacent catalytic domains. Here, we report 100-fold activation of natriuretic peptide receptors in the absence of ATP. Addition of a nonhydrolyzable ATP analog had no effect at early time periods (seconds) but increased cGMP production about two-fold after longer incubations (minutes), consistent with a stabilization, not activation, mechanism. These data indicate that ATP does not activate natriuretic peptide receptors. Instead, ATP increases activity primarily by maintaining proper receptor phosphorylation status, but also serves a previously unappreciated enzyme stabilizing function.

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Correspondence to Lincoln R Potter.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Antos, L.K., Abbey-Hosch, S.E., Flora, D.R. et al. ATP-independent activation of natriuretic peptide receptors. BMC Pharmacol 5, P3 (2005). https://doi.org/10.1186/1471-2210-5-S1-P3

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  • DOI: https://doi.org/10.1186/1471-2210-5-S1-P3

Keywords

  • Natriuretic Peptide
  • Brain Natriuretic Peptide
  • Atrial Natriuretic Peptide
  • Peptide Binding
  • Receptor Phosphorylation