gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Meprin A is involved in the degradation of brain natriuretic peptide in mice

Meprin A ist beteiligt am Abbau von Brain Natriuretic Peptide in der Maus

Meeting Abstract

  • K. Pankow - Forschungsinstitut für Molekulare Pharmakologie (Berlin, D)
  • X. Sun - Forschungsinstitut für Molekulare Pharmakologie (Berlin, D)
  • G. Krause - Forschungsinstitut für Molekulare Pharmakologie (Berlin, D)
  • W.E. Siems - Forschungsinstitut für Molekulare Pharmakologie (Berlin, D)
  • T. Walther - Erasmus Medical Center, Rotterdam

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP127

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Pankow et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Natriuretic peptides (NP) like atrial (ANP) and B-type (BNP) natriuretic peptide are cyclic peptide hormones mainly of cardiac origin with natriuretic and vasodilator effects. NP are quickly cleared from circulation by (a) binding to a clearance receptor with the subsequent internalization and cleavage by cytoplasmic enzymes and (b) degradation by extracellular peptidases. The neutral endopeptidase (NEP), a membrane bound type-II metallopeptidase of the M13 family, is generally regarded to be the main enzyme for NP-degradation. However, our own studies with membranes of wildtype and NEP-knockout mice showed BNP resistance for NEP degradation and thus BNP-degrading activity independent from NEP.

In this study we investigated which peptidase is responsible for the mouse BNP degradation in murine kidney using class-specific inhibitors. The BNP-degrading activity was completely inhibited by the metalloprotease inhibitor EDTA, but not by phosphoramidon, which inhibits e.g. NEP, NEP2 and endothelin-converting enzyme. Further investigations with specific metalloendoproteinase inhibitors enabled us to identify meprin A (EC as a promising candidate degrading BNP. Meprin A is a phosphoramidon- insensitive multimeric metalloprotease expressed in the brush borders of kidney proximal tubules that hydrolyzes a variety of growth factors, vasoactive peptides, cytokines and extracellular matrix proteins. Both murine kidney membrane and purified meprin A cleaved within the N-terminal tail of mouse BNP at position His6-Ile7. Actinonin, the most effective inhibitor for meprin A, totally blocked the mouse BNP degradation in murine kidney membranes. Interestingly, the resulting peptide BNP 7-32 appears to be accessible for degradation by NEP. Thus, the initial degradation step by meprin A is essential for the rapid BNP catabolism. As BNP elevation is discussed as a therapeutic tool in the treatment of chronic heart failure, the understanding of its metabolism is important for the development of new therapeutic strategies. Consequently, the inhibition of meprin A could be a new potential method to increase circulating BNP levels.