A Comparative Study of Kinin, Kallidin, and Bradykinin

Abstract

Partially purified kinin, a polypeptide in wasp venom, has been found to be a potent smoothmuscle stimulating and hypotensive agent. Such a preparation was 10 to 100 times more effective than histamine in enhancing capillary permeability on intradermal injection, and 10 times more effective than acetylcholine in evoking pain on a cutaneous blister base. Silva, 1955) are potent polypeptides, with many properties in common. All are known to produce a characteristic delayed slow contraction of the isolated guinea-pig ileum, and to lower markedly the arterial blood pressure of the rabbit and cat on intravenous injection. They are stable in neutral or acidic, but not in alkaline, solution; they are insoluble in anhydrous acetone or ether, and are rapidly inactivated by chymotrypsin. Kinin occurs in large quantities, together with histamine and 5-hydroxytryptamine, in the venom of the common wasp (V. vulgaris); kallidin and bradykinin are released from the a1 globulin fraction of serum by the action of kallikrein and trypsin (or B. jararaca venom) respectively. In view of their similar properties it was of interest to extend previous studies of these three substances and to compare their properties under the same conditions. Preliminary results of such a comparison have been reported to the Physiological Society (Holdstock, Mathias and Schachter, 1956).In the present experiments kinin has been further purified and characterized chemically and pharmacologically. It has been found to be extremely effective in enhancing capillary permeability and in evoking cutaneous pain on application to a blister base. Kallidin and bradykinin were also shown to increase capillary permeability. The different methods of preparing kallidin and bradykinin were compared, and some modifications of previous methods are described.Despite their many common properties, kinin has been definitely distinguished from kallidin and bradykinin. The latter two substances, however, were not successfully distinguished by pharmacological or chemical tests, and must be closely similar, or possibly identical, compounds. MEMODSIsolated Smooth Muscle and Arterial Blood Pressure. Preparations of guinea-pig ileum, rabbit intestine, and rat uterus were suspended in Tyrode solution in an 18 ml. bath. Guinea-pig and rabbit intestine were kept at 34 to 36°C. and rat uterus (anoestrous) at 26 to 280 C., the latter temperature being required to eliminate spontaneous activity in this preparation. Atropine (0.2 ,ug.) and mepyramine (0.4 jsg.) were added to the bath before each test, except when assaying for histamine, in which case mepyramine was omitted. Usually the polypeptide was in contact with the tissue for 60 sec.Dogs were anaesthetized by intravenous injection of a mixture of chloralose (50 mg./kg.) and urethane (500 mg./kg.); rabbits received pentobarbitone sodium (30 mg./kg.) intravenously, supplemented by ether. The substances tested were injected into the femoral vein and the arterial blood pressure was recorded with a mercury manometer from a carotid a...

Human Urinary Kinin Excretion

“…Wasp kinin (Jacques and Schachter, 1954;Schachter and Thain, 1954) and the plasma kinins are very similar; but wasp kinin is inactivated by trypsin and can be separated from the plasma kinins by paper chromatography (Holdstock et al, 1957 …”

“…They include the substances kallidin (Werle, 1937;Werle and Berek, 1950), bradykinin (Rocha e Silva, Beraldo and Rosenfeld, 1949) and the pain-producing substance Stewart, 1954, 1957). There is some evidence that the same active principle may be responsible for the activity of all these substances (Werle, 1953;Jepson, Armstrong, Keele, and Stewart, 1956;Holdstock, Mathias and Schachter, 1957), and possibly also for the activity of various other bradykinin-like substances which have been reported Lewis, 1955, 1956 ;Schachter, 1956;Adam, Hardwick, and Spencer, 1957;Lewis and Work, 1957;Lewis, 1958). Human urine contains a similar kinin which could not be distinguished from the plasma kinins qualitatively or by parallel assays (Gomes, 1955;Gaddum and Horton, 1959) though there is some chemical evidence that the active principles are different (Gomes, 1957).…”

The Chromatographic Behaviour of Wasp Venom Kinin, Kallidin and Bradykinin

“…The R F of wasp kinin has been either zero or very low in all solvents hitherto employed for its chromatography on paper (Holdstock et al, 1957 …”

“…-Ascending paper chromatograms were run at room temperature on Whatman No. 1 paper and the eluates tested on the isolated rat uterus and guinea-pig ileum as previously described (Holdstock et al, 1957). The solvents used were:…”

“…All three substances appear to be polypeptides. They produce a characteristic slow contraction of isolated smooth muscle, are vasodilator agents, increase capillary permeability and cause pain when applied to the exposed blister base of human skin (Holdstock, Mathias, and Schachter, 1957 Holdstock et al (1957). The bradykinin preparation contained 1 unit (Rocha e Silva, Beraldo and Rosenfeld, 1949) in 140 1-g. of dry material; 120 pg.…”