In vitro degradation of endothelin-1 by endopeptidase 24.11 (enkephalinase).
The breakdown of endothelin-1 by crude membrane preparations of human kidney and choroid plexus was investigated. 125I-labeled endothelin-1 was degraded by both tissues in a phosphoramidon-sensitive way, suggesting a role of endopeptidase 24.11 in the in vitro metabolism of this peptide. Identification of the cleavage sites of purified human renal endopeptidase 24.11 in the sequence of endothelin-1 revealed that bonds involving the amino side of the hydrophobic amino acids (Ser4, Leu6, Val12, Phe14, His16, Leu17, Ile19) were susceptible to cleavage. Endothelin-1 appears thus to be degraded at multiple sites by endopeptidase 24.11 in vitro, producing inactive fragments.
Fagny
C
C
Laboratoire Pluridisciplinaire de Recherche Expérimentale Biomédicale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Michel
A
A
Léonard
I
I
Berkenboom
G
G
Fontaine
J
J
Deschodt-Lanckman
M
M
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002831:Choroid Plexus / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D016232:Endothelins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction
D000596:Amino Acids; D016232:Endothelins; D015260:Neprilysin