The effects of novel cathepsin E inhibitors on the big endothelin pressor response in conscious rats.
The aspartic protease, cathepsin E, has been shown to specifically cleave big endothelin (big ET-1) at the Trp21-Val22 bond to produce endothelin (ET-1) and the corresponding C-terminal fragment. To determine whether cathepsin E is a physiologically relevant endothelin converting enzyme (ECE), three novel and potent inhibitors of cathepsin E were administered to conscious rats prior to a pressor challenge with big ET-1. One of the inhibitors of cathepsin E, SQ 32,056 (3 mg/kg i.v.), blocked the big ET-1 response. However, this dose of SQ 32,056 also blocked the pressor response to ET-1. Phosphoramidon specifically inhibited the Big ET-1 pressor response. These results suggest that ECE is not cathepsin E.
Bird
J E
JE
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ.
Waldron
T L
TL
Little
D K
DK
Asaad
M M
MM
Dorso
C R
CR
DiDonato
G
G
Norman
J A
JA
D000595:Amino Acid Sequence; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D020059:Cathepsin E; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D016232:Endothelins; D006020:Glycopeptides; D009842:Oligopeptides; C072249:SQ 32602; C072248:SQ 32056; D000803:Angiotensin I; D002403:Cathepsins; D020059:Cathepsin E; C008890:phosphoramidon; D009638:Norepinephrine