Human brain contains a metalloprotease that converts big endothelin-1 to endothelin-1 and is inhibited by phosphoramidon and EDTA.
Incubation of big endothelin-1 (bET-1) with protein derived from the detergent-extracted 100,000 g pellet prepared from human brain tissue resulted in the formation of endothelin-1 (ET-1) at a rate of 90 fmol mg-1 protein min-1. This formation was inhibited in a concentration-dependent manner by either phosphoramidon or EDTA, with half-maximal inhibitory concentrations of 2 and 20 microM, respectively. No conversion of big endothelin-3 (bET-3) to endothelin-3 (ET-3) was detected under the same conditions. These results show the presence in the human brain of a metalloprotease-like enzymatic activity which selectively converts bET-1 and ET-1. Together with earlier reports of mRNA for ET-1 this suggests the presence of the entire synthetic pathway for ET-1 in human brain.
Warner
T D
TD
Northwestern University Medical School, Chicago, IL 60611.
Schmidt
H H
HH
Kuk
J
J
Mitchell
J A
JA
Murad
F
F
D001921:Brain / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology*; D019332:Endothelin-1; D016232:Endothelins / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D008666:Metalloendopeptidases / Q000032:analysis* / Q000037:antagonists & inhibitors; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011498:Protein Precursors / Q000378:metabolism*
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D004492:Edetic Acid; D008666:Metalloendopeptidases; D015260:Neprilysin; C008890:phosphoramidon