Role of the endopeptidase 24. 11 in the disposition and metabolism of endogenous atrial natriuretic factor in the rabbit

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Drug Metabolism and Disposition; (USA)

OSTI ID:5735610

Marleau, S; Nguyen, T T; Du Souich, P; Bellemare, M; De Lean, A; Ong, H ^[1]

---

1. Universite de Montreal, Quebec (Canada)

The neutral endopeptidase 24.11 (NEP) has been shown to inactivate the atrial natriuretic factor (ANF) by opening the ring structure. To document the role of NEP in the metabolic fate of ANF in vivo, the effects of an infusion of thiorphan (25 micrograms/min/kg), a specific NEP inhibitor, on the kinetics and metabolism of endogenous ANF were studied in conscious rabbits. A bolus of ({sup 125}I)ANF(99-126) was injected 50 min after the beginning of the infusion of thiorphan. Plasma samples containing the radioactive peptides were separated by reverse-phase HPLC. The parent compound could be separated from at least two other minor metabolites, corresponding to the elution position of ({sup 125}I)ANF(99-105/106-126), the inactive ring-opened metabolite, and of ({sup 125}I)ANF(103-126), an N-truncated analog. The generation of the N-truncated metabolite was increased by thiorphan. Thiorphan also induced an increase in plasma ANF (29%) that was closely associated with a 32% reduction in the systemic clearance of ({sup 125}I)ANF(99-126), whereas no modification in the estimated secretion rate was detected. These results support a role for NEP in the regulation of endogenous ANF plasma levels. These results also suggest that specific inhibition of NEP may result in an increase in the apparent activity of alternative metabolic pathways.

• OSTI ID: 5735610
• Journal Information: Drug Metabolism and Disposition; (USA), Journal Name: Drug Metabolism and Disposition; (USA) Vol. 19:1; ISSN DMDSA; ISSN 0090-9556
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOASSAY
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HYDROLASES
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PEPTIDES
PROTEINS
RABBITS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIOISOTOPES
SEPARATION PROCESSES
TRACER TECHNIQUES
VERTEBRATES