Development of competitive antagonists of bradykinin.

Abstract

Development of adequate tools for study of biological phenomena frequently requires long periods of time, and progress in the kallikrein-kinin field has been no exception to this generalization. It is now more than six decades since the original evidence for the kinin system was published by E. K. Frey (1926) and more than 25 years since the structure of bradykinin was elucidated. During these years many investigators have produced increasing amounts of evidence demonstrating the incredible complexity of kinin physiology and pathology and the many interactions of the kinin system with several other physiological regulatory systems. In several cases it has been suggested or inferred that kinins may be involved in a particular physiological process, but without adequate tools to address the problem, these ideas have remained untested. In such complex situations specific, selective inhibitors are essential to elucidation of the mechanisms involved. In the kinin field the only inhibitors available until recently have been kallikrein inhibitors. The most widely used of these, aprotinin, while useful against plasma kallikrein, is not very effective against tissue kallikrein, the more important enzyme in many kinin-related processes.