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  • Poster presentation
  • Open Access

ATP-independent activation of natriuretic peptide receptors

  • 1,
  • 1,
  • 1 and
  • 1Email author
BMC Pharmacology20055 (Suppl 1) :P3

  • Published:


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

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.

Authors’ Affiliations

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, USA


© BioMed Central Ltd 2005