In vivo metabolism of brain natriuretic peptide in the rat involves endopeptidase 24. 11 and angiotensin converting enzyme

Journal Article · Fri Nov 30 00:00:00 EST 1990 · Biochemical and Biophysical Research Communications; (USA)

DOI:https://doi.org/10.1016/S0006-291X(05)81051-4· OSTI ID:6323678

Vanneste, Y; Pauwels, S; Lambotte, L; Deschodt-Lanckman, M ^[1]

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1. Universite Libre de Bruxelles (Belgium)

The metabolism of brain natriuretic peptide (BNP) was studied in rats infused with 125I-BNP. During the infusion, the intact peptide was progressively converted to labelled degradative products, separated into nine peaks of radioactivity on HPLC, and accounting for approximately 70% of total plasma radioactivity at the plateau phase. After stopping the infusion, intact BNP disappeared with a half-life of 1.23 +/- 0.35 min whereas the labelled fragments accounted for progressively greater proportion of total activity. The degradation of BNP was significantly reduced by phosphoramidon (t1/2, 11.28 +/- 0.49 min) and captopril (t1/2, 6.99 +/- 0.34 min). A maximal effect was observed when both protease inhibitors were given simultaneously (t1/2, 15.3 +/- 0.48 min). When 125I-BNP was incubated in vitro with purified endopeptidase 24.11 (E-24.11) and angiotensin-converting enzyme (ACE), there was a time-dependent disappearance of the intact peptide associated with the generation of six labelled fragments, corresponding to fragments found in vivo. In serum the peptide was rapidly degraded with a half-life of 4.6 +/- 0.1 min, and the pattern of labelled fragments was similar to that observed during in vitro incubation with ACE. Captopril significantly reduced the rate of degradation of BNP in serum. The results allow to associate two define enzyme activities, namely E-24.11 and ACE, with the metabolism of BNP in vitro. They also indicate that, despite a close homology between ANP and BNP, the two peptides undergo different pathways of clearance.

• OSTI ID: 6323678
• Journal Information: Biochemical and Biophysical Research Communications; (USA), Vol. 173:1; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PEPTIDE HYDROLASES
ENZYME ACTIVITY
PEPTIDES
METABOLISM
BIOLOGICAL HALF-LIFE
BIOLOGICAL PATHWAYS
BRAIN
ENZYME INHIBITORS
IODINE 125
LIQUID COLUMN CHROMATOGRAPHY
RATS
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RODENTS
SEPARATION PROCESSES
VERTEBRATES
550501* - Metabolism- Tracer Techniques