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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 BNP1-32 when added individually or in combination, respectively. In contrast, neither inhibitor alone or in combination prevented the inactivation of human BNP1-32 by human kidney membranes. Leupeptin, a serine protease inhibitor, totally blocked inactivation of human BNP by human membranes, substantially blocked the inactivation of rat BNP1-32 by human membranes, but had no effect on the inactivation of rat BNP1-32 by rat kidney membranes. Purified neprilysin reduced the bioactivity of rat BNP1-32 and human BNP. Digestion with both meprin and neprilysis caused the greatest reduction in rat BNP1-32 but had no effect on the bioactivity of human BNP1-32. We conclude that meprin A does not degrade BNP in humans and should not be considered a pharmacologic target of the natriuretic peptide system.

Original languageEnglish (US)
Pages (from-to)1007-1011
Number of pages5
JournalBiochemical Pharmacology
Volume80
Issue number7
DOIs
StatePublished - Oct 1 2010

Fingerprint

meprin A
Brain Natriuretic Peptide
Rats
Neprilysin
Membranes
Peptide Hydrolases
Kidney
Bioactivity
Tiopronin
Natriuretic Peptides
Serine Proteinase Inhibitors
Bioassay
Blood pressure
Protease Inhibitors

Keywords

  • B-type natriuretic peptide (BNP)
  • CGMP
  • Guanylyl cyclase receptor A (GC-A)
  • Natriuretic peptide
  • Natriuretic peptide receptor A (NPR-A)
  • Natriuretic peptide receptor B (NPR-B)

Cite this

Human B-type natriuretic peptide is not degraded by meprin A. / Dickey, Deborah M.; Potter, Lincoln R.

In: Biochemical Pharmacology, Vol. 80, No. 7, 01.10.2010, p. 1007-1011.

Research output: Contribution to journalArticle

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