D. The kinin system A history and review of the kinin system

Abstract

The first two plasma systems, clotting and fibrinolysis, we have so far dealt with in this meeting emerged largely from an analysis of clinically obvious end-results. The kinin system differs in two respects: first, it emerged largely from studies of laboratory artifacts which suggested that a number of pharmacologically active substances could be derived from plasma; and secondly, in that the biological significance of its end results, whether physiological or pathological, is in most instances still a matter for conjecture. This pharmacological odyssey has been concerned with studies of four biological effects. Two were on blood vessels, namely vasodilatation, which when induced systemically is manifested as hypotension, and increased permeability of the walls of capillaries and venules to plasma proteins. The third effect is contraction of certain kinds of smooth muscle which, since the rat uterus is the most commonly used for in vitro tests, we may call uterotonic; and the fourth as Professor Keele and his colleagues first demonstrated, is the production of pain. All these four effects may be induced by the end product of the plasma system—the kinins. As with many other biological systems, the haphazard discovery of the different elements of the kinin system has engendered an almost equally haphazard growth of terminology, and there is not yet a generally agreed rationalization of the terms in use. But at least the term ‘kinin’ is general enough not to offend the claims either of priority or logic; and covers a group of unbranched polypeptides containing some nine to eleven amino acid residues. Kinins are formed by enzyme action on proteins, and we may with equally inoffensive generality call the substrate from which they are split off ‘kininogens’, and the enzymes which do the splitting, ‘kininogenases’.