Plasma kinins

Cell Surface Assembly of the Plasma Kinin-Forming Cascade... 

Neurotensin 11, which was isolated from bovine small intestine by Carraway and Leeman 29) in 1973, causes, in addition to the typical plasma kinin effects (lowering of the blood pressure, contracting action on the intestine and uterus), an increase in the LH and FSH secretion without influencing the release of somatotropin or thyrotropin. 

Plasma kinins are tissue hormones liberated from a-globulins of the blood plasma by kallikrein. 

Eisen, V., Enzymic Aspects of Plasma Kinin Formation, Proc. Royal Soc. 

Human Plasma. IV. The Interrelationship between the Contact Phase of Blood Coagulation and the Plasma Kinin System in Man, Thrombos. Diathes. Haemorrh. (1972) 27, 141. 

The authors cited evidence that the kallikrein/kinin system is involved in cold urticaria, that ACE inhibitors increase wheal-and-flare reactions to cutaneously applied bradykinin, and that ACE inhibitor therapy is associated with raised plasma kinin concentrations. They therefore recommended avoidance of ACE inhibitors in patients with cold urticaria. 

A possible explanation for the anti-inflammatory action of cortisol based on the prevention of release of plasma kinins has been published. A number of 8-dehydro analogs of corticosteroids have been synthesized and their thymolytic and salt retaining properties measured. The compound found to have the highest thymolytic activity was 1 (11.4 x hydrocortisone). Again the fallacy of projecting biological activity from one series of steroids to another was demonstrated by the large decrease in activity exhibited by the 8-dehydro steroid 2 as compared with 16a-methylprednisolone (3). 

Angiotensinogen (from liver) Blocked by ACE inhibitors Renin (kidney) ensin 1 Brad Angiotensin-Converting Enzyme (plasma) /kinin... 

The plasma kinins kallidin and bradykinin are generated by the organic kaiiikrein released from glands and tissue or the serum kaiiikrein generated in blood from prekallikrein. Due to the vasodilator effect of plasma kinins, the kinin-generating... 

A vasodilating peptide with smooth-muscle stimulating action was described by Rocha e Silva, Beraldo and Rosenfeld in 1949 and named bradykinin. It is produced by the action of trypsin or snake venoms on plasma. A similar substance, kallidin, was prepared shortly afterwards by Werle and Berek using the protease kalUkrein. Other peptides with similar properties have been described and the general term kinins or, when derived from plasma proteins, plasma kinins has been recommended. The best-known kinin, bradykinin, has recently been shown to be a nonapeptide, and its structure confirmed by synthesis - . When injected subcutaneously into laboratory animals and man, bradykinin causes vasodilatation, increased vascular permeability, leucocyte infiltration and pain. 

INFLAMMATION Kinins participate in a variety of inflammatory diseases. Plasma kinins increase permeability in the microcirculation. The effect, like that of histamine and serotonin in some species, is exerted on the small venules and involves separation of the junctions between... 

Not fully established, but it is believed that SPPS contains low levels of pre-kallikrein activator, which stimulates the production of bradykinin, which can cause vasodilatation and hypotension. Normally the bradykinin is destroyed by kininase II (ACE), but this is delayed by the ACE inhibitor so that the hypotensive effects are exaggerated and prolonged. In the case with albumin 4%, a sample of the albumin used was analysed, and it was found to contain less prekallikrein activating factor than maximum permissible levels. It was suggested that the infusion of gelatin-based colloids somehow resulted in raised plasma kinin levels associated with inhibition of ACE. ... 

D.F. Elliott, G.P. Lewis, E.W. Horton, The structure of bradykinin—a plasma kinin from ox blood. Biochem. Biophys. Res. Commun. 3 87-91 (1960)... 

There are 3 known plasma kinins, namely the nonapeptide bradykinin or kallidin-9 [154, 157, 158, 363, 364, 473, 523], lysyl-bradykinin or kaUidin-10 [499,665] and methionyl-lysyl-bradykinin [155,159,556]. These pharmacologically active polypeptides behave simlarily, although quantitative differences exist between them [141, 156, 412]. Bradykinin increases vascular permeability in the rat after intradermal injection [82,107,167,633] and also after sub-plantar injection into the paw [110, 210, 389, 601], and as such plasma kinins are potential mediators of the anaphylactoid oedema. 

The plasma kinin precursor may pass into the inflamed regions as a result of the increased vascular permeability produced by primary mediators of the anaphylactoid reaction. Activation of kininogen might then occur through dilution in oedema fluid or by contact with damaged and foreign tissue surfaces. Moreover, the pH of inflamed interstitial fluid and exudate is slightly acid [195, 422, 450-452, 546] and kininase activity may thus be inhibited [149, 700]. Such conditions would favour the accumulation of released kinins at interstitial... 

Anaphylactoid-inducing agents such as ovomucoid, dextrin and dextran fail to induce a release of kinin from plasma in vitro, although dextran sulphate elicits kinin release under similar conditions but fails to increase vascular permeability in vivo [31]. It is interesting that although ovomucoid is an active anaphylactoid-inducing agent, it is also an inhibitor of the proteolytic formation of plasma kinins. Evidence to date indicates that an important role for plasma kinins in the mediation of the anaphylactoid reaction is doubtful. 

H.Edery and G.P.Lewis, Plasma Kinin-Forming-Enzyme Activity in Lymph after Injury, J. Physiol., Lond. 163, 48-49P (1962). 

Several other substances which have hormone-like activity are widely distributed and exert their effects in the area in which they are produced. Histamine, serotonin and various plasma kinins may be considered to be local hormones. 

Wilkens, H., and Back, N. Bronchoconstriction and apnea in canine anaphylaxis Role of histamine and plasma-kinins. Fed. Proc. 26 785, 1967. 

Greenbaum, L.M. and Yamafuji, K. (1966). The in vitro inactivation and formation of plasma kinins by spleen cathepsins. Brit.J.Pharmacol., 27, 230-238. 

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