POSTSTATIN, A NOVEL INHIBITOR OF BRADYKININ-DEGRADING ENZYMES IN RAT URINE

被引:31
作者
MAJIMA, M
SHIMA, C
SAITO, M
KURIBAYASHI, Y
KATORI, M
AOYAGI, T
机构
[1] Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa
[2] Institute of Microbial Chemistry, Shinagawa, Tokyo, 141
关键词
POSTSTATIN; BRADYKININ; DEGRADATION PATHWAY; URINE; KININASE;
D O I
10.1016/0014-2999(93)90772-A
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Incubation of bradykinin with rat urine resulted in the successive degradation of bradykinin to bradykinin-(1-8), bradykinin-(1-7) and bradykinin-(1-6). In contrast, in rat plasma, bradykinin was degraded via either bradykinin-(1-8) or bradykinin-(1-7) to bradykinin-(1-5). Phosphoramidon (1 mM) partially inhibited the degradation of bradykinin by rat urine, as well as the conversion of bradykinin-(1-7) to bradykinin-(1-6). D,L-2-Mercaptomethyl-3-guanidinoethylthiopropanoic acid (1 mM) and captopril (1 mM) did not have a significant effect on any of the degradation steps in rat urine. In contrast, all of the degradation steps in urine, namely, from bradykinin to bradykinin-(1-8), from bradykinin-(1-8) to bradykinin-(1-7) and from bradykinin-(1-7) to bradykinin-(1-6), were markedly inhibited by poststatin (1 mM), even though this compound was reported originally to be a novel inhibitor of post-proline cleaving enzyme. Poststatin (I mM) did not inhibit the degradation of bradykinin in rat plasma. These results indicate that poststatin is an effective inhibitor of kinin-degrading enzyme in rat urine.
引用
收藏
页码:181 / 190
页数:10
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