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Internalization and degradation of natriuretic peptide receptor-A is stimulated by ligand binding

Background

Natriuretic peptide receptor-A (NPR-A) is a transmembrane receptor guanylyl cyclase that binds and mediates the effects of atrial and B-type natriuretic peptides (ANP/BNP). Internalization and ligand-dependent degradation of NPR-A is controversial, in part due to the use of ligand binding studies to predict the cellular location of the receptor. Here, we used a more direct sequential immunoprecipitation-western blot assay to demonstrate that long-term ANP exposure increases NPR-A degradation in primary, immortalized, and transfected cells.

Results

A separate novel extracellular epitope antibody-binding assay indicated that NPR-A is internalized under basal conditions and that this rate is increased about two-fold by ANP exposure. siRNA knock down of clathrin and dominant negative inhibition of dynamin failed to inhibit ANP-dependent NPR-A degradation, whereas dominant negative dynamin expression reduced the rate of NPR-A internalization about 40%.

Conclusion

These data indicate that NPR-A is basally internalized by a dynamin-dependent pathway and that prolonged ANP exposure stimulates both NPR-A internalization and degradation.

Acknowledgements

D.R.F. was supported by an award from the American Heart Association (0815607G).

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Correspondence to Darcy R Flora.

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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 2.0 International 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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Flora, D.R., Conner, S.D. & Potter, L.R. Internalization and degradation of natriuretic peptide receptor-A is stimulated by ligand binding. BMC Pharmacol 9, P14 (2009). https://doi.org/10.1186/1471-2210-9-S1-P14

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Keywords

  • Peptide
  • Ligand Binding
  • Natriuretic Peptide
  • Cellular Location
  • Binding Study