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BMC Pharmacology

, 9:P14 | Cite as

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

  • Darcy R Flora
  • Sean D Conner
  • Lincoln R Potter
Open Access
Poster presentation
  • 1.4k Downloads

Keywords

Peptide Ligand Binding Natriuretic Peptide Cellular Location Binding Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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.

Notes

Acknowledgements

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

Copyright information

© Flora et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • Darcy R Flora
    • 1
  • Sean D Conner
    • 2
  • Lincoln R Potter
    • 1
    • 3
  1. 1.Department of PharmacologyUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of Genetics, Cell Biology and DevelopmentUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of Biochemistry, Molecular Biology and BiophysicsUniversity of MinnesotaMinneapolisUSA

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