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
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Keywords

Peptide Ligand Binding Natriuretic Peptide Cellular Location Binding Study 

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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