Open AccessAn Orally Active Chymase Inhibitor, BCEAB, Suppresses Heart Chymase Activity in the Hamster
Author(s) -
Shinji Takai,
Denan Jin,
Masato Sakaguchi,
Kazuyoshi Kirimura,
Mizuo Miyazaki
Publication year - 2001
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.86.124
Subject(s) - chymase , hamster , lisinopril , chemistry , ic50 , renin–angiotensin system , pharmacology , enzyme inhibitor , in vivo , angiotensin ii , elastase , angiotensin converting enzyme , ace inhibitor , endocrinology , medicine , biochemistry , enzyme , in vitro , biology , receptor , blood pressure , microbiology and biotechnology
We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-[[bis-(4-methyl-phenyl)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 microM lisinopril was 2.8 microM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.