Effects of daphnodorin A, daphnodorin B and daphnodorin C on human chymase-dependent angiotensin II formation.
We investigated whether daphnodorin A, daphnodorin B and daphnodorin C inhibited human chymase-dependent angiotensin II-forming activity. Although the structures of these compounds are very similar, daphnodorin A completely inhibited angiotensin II formation generated by chymase, while daphnodorin B partially inhibited and daphnodorin C did not. On the other hand, these daphnodorins did not affect angiotensin converting enzyme-dependent angiotensin II formation. Furthermore, these daphnodorins did not inhibit purified human tryptase, which, like chymase, is contained in mast cells. Therefore, daphnodorin A, but not daphnodorin B and daphnodorin C, may specifically inhibit the chymase-dependent angiotensin II formation, and such differences between inhibitory effects of these compounds to human chymase may be useful for the development of human chymase inhibitor.
Takai
S
S
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan. pha010@art.osaka-med.ac.jp
Sakaguchi
M
M
Jin
D
D
Baba
K
K
Miyazaki
M
M
D000328:Adult; D000804:Angiotensin II / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D053818:Chymases; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001578:Benzopyrans; D015842:Serine Proteinase Inhibitors; D000804:Angiotensin II; C055028:daphnodorin B; C055027:daphnodorin A; C055029:daphnodorin C; D012697:Serine Endopeptidases; D053818:Chymases