1. Academic Validation
  2. Human B-type natriuretic peptide is not degraded by meprin A

Human B-type natriuretic peptide is not degraded by meprin A

  • Biochem Pharmacol. 2010 Oct 1;80(7):1007-11. doi: 10.1016/j.bcp.2010.06.015.
Deborah M Dickey 1 Lincoln R Potter


  • 1 Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.

B-type natriuretic peptide (BNP) combats cardiac stress by reducing blood pressure and ventricular fibrosis. Human BNP is inactivated by unknown cell surface proteases. N-terminal cleavage of mouse BNP by the renal protease meprin A was reported to increase inactivating degradation by a second protease named Neprilysin. Since the sequence surrounding the meprin A cleavage site in BNP differs between species, we tested whether meprin A degrades human BNP. Using a recently developed proteolytic bioassay, the ability of various Protease Inhibitors to block the inactivation of BNP was measured. In rat kidney membranes, inhibitors of meprin A or Neprilysin partially or completely blocked inactivation of rat BNP(1-32) when added individually or in combination, respectively. In contrast, neither inhibitor alone or in combination prevented the inactivation of human BNP(1-32) by human kidney membranes. Leupeptin, a serine protease inhibitor, totally blocked inactivation of human BNP by human membranes, substantially blocked the inactivation of rat BNP(1-32) by human membranes, but had no effect on the inactivation of rat BNP(1-32) by rat kidney membranes. Purified Neprilysin reduced the bioactivity of rat BNP(1-32) and human BNP. Digestion with both meprin and neprilysis caused the greatest reduction in rat BNP(1-32) but had no effect on the bioactivity of human BNP(1-32). We conclude that meprin A does not degrade BNP in humans and should not be considered a pharmacologic target of the natriuretic peptide system.