Participation of neutral endopeptidase 24. 11 (NEP; enkephalinase A) in kinin metabolism in vitro and in vivo

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6943145

Ura, N; Carretero, O A; Erdoes, E G

Studies were done in 2 phases in rats. (1) Bradykinin was added catheter-collected urine, and its hydrolysis was determined by RIA. Three different kiniases were found by application of specific inhibitors. Kininase I-type carboxypeptidase was inhibited by 2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid, kiniase II by captopril and NEP by phosphoramidon (PA). Surprisingly, NEP was responsible for 68% of total kininase, while kininase I and II contributed only 9 and 23%. (2) To study the effects of inhibition of NEP on renal function, rats were infused with PA (330 ..mu..g/hr/kg, n=6). Urinary kinin level, kininase, GFR, RBF, U/sub Na/V, U/sub K/V and UV were measured. PA decreased total urinary kininase activity from 284 to 58 ng/min/kg (77%, p < 0.01) and increased urinary kinin excretion from 74 to 128 pg/min/kg (73%, p < 0.02), UV from 72 to 82 ..mu..l/min/kg (15%, p < 0.01) and U/sub Na/V from 12 to 17 ..mu.. Eq/min/kg (37%, p < 0.02). PA did not change BP, RBF, GFR or U/sub K/V. /sup 125/I-Tyr-bradykinin infused into the aorta did not appear in urine intact during PA administration. In conclusion, this is the first demonstration of NEP catabolizing kinins in vivo; its inhibition increased the excretion of intrarenally generated kinins. Changes in water and electrolyte excretion may be caused by kinins generated in the distal nephron.

• Research Organization: Henry Ford Hospital, Detroit, MI
• OSTI ID: 6943145
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
BRADYKININ
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
FUNCTIONS
HYDROLASES
IN VITRO
IN VIVO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KININS
MAMMALS
MATERIALS
METABOLISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RATS
RODENTS
TRACER TECHNIQUES
URINE
VERTEBRATES
WASTES