Inhibition of Df-protease--induced kinin release by synthetic inhibitors.
A protease (Df-protease) from house dust mite (D. farinae) is closely associated with mite-induced allergy: Df-protease has a similar substrate specificity to blood coagulation factor XIIa and catalyzes the activation of kallikrein-kinin system in human plasma. With the purpose of prevention of kinin-formation in plasma by Df-protease, inhibition of Df-protease with synthetic inhibitors was tested in vivo and in vitro. Among the inhibitors, including amidine and guanidine derivatives, N-allyl-N-[4-(4-amidinophenoxycarbonyl)-alpha-methylcinnamoyl++ +]glycine ethyl ester mesylate was the most effective to inhibit Df-protease with Ki = 9 x 10(-9) M and also to prevent kinin-release from Df-protease in human plasma. Enhancement of vascular permeability in guinea pigs caused by kinin-release was stoichiometrically suppressed by the inhibitor.
Noguchi
Y
Y
Toin Human Science and Technology Center, Department of Material Science and Technology, Toin University of Yokohama, Japan.
Matsushima
A
A
Ohmura
R
R
Ichinose
T
T
Nakai
H
H
Kodera
Y
Y
Inada
Y
Y
D000578:Amidines / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D006146:Guanidines / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007700:Kinetics; D007705:Kinins / Q000378:metabolism*; D008925:Mites / Q000201:enzymology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000578:Amidines; D006146:Guanidines; D007705:Kinins; D015842:Serine Proteinase Inhibitors; C099397:Df protease; D012697:Serine Endopeptidases