Kinin formation

Fields T, Ghebrehiwet B, Kaplan AP Kinin formation in hereditary angioedema plasma evidence against kinin derivation from C2 and in support of spontaneous formation of bradykinin. J Allergy 82 Chn Immunol 1983 72 54-60. 

Bik decreases ischemia/reperfusion injury by inhibiting proteases that cause kinin release [4, 99]. Reversion to a normal blood pressure occurs in two ways through inhibition of kallikrein with protease inhibitors and by destruction of kinins by kinase. Bik decreases kinin formation through their effect on kallikrein. The duration of kinin formation and destruction ranges from 2 to 30 min [100, 101]. After 30 min, little kinin activity is detectable. As inflammation abates, so does neutrophil chemotaxis and endothelial adherence to the basement membrane. PAR also regulates vascular tone and participates in response to vascular injury. Bik inhibits PAR activation [79, 80],... 

Figure 6. Triggering of kinin formation, blood coagulation, and fibrinolysis through specific proteolytic activation of the Hageman Factor (Factor XII). In the cascades, the factor on the left side of the reaction (zymogen) is converted to an active enzyme by proteolysis. PL = phospholipids.

Kinin formation Causes vasodilation Prolongs inflammation... 

Proud D, Kaplan AP Kinin formation mechanisms and role in inflammatory disorders. Annu. Rev. Immunol. 1988 6 49-83. 

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

Thi ,DPhe BK [Thi ,DPhe ]-bradykinin. bradykinin-potentiating peptide teprotide. bradykinin potentiator B teprotide. BRADYKININ RECEPTOR AGONISTS act at sites recognizing members and derivatives of the bradykinin family of hormone peptides - kinins - of which bradykinin (BK) and kallidin (lysyl-bradykinin Lys-BK KD) are the main mammalian members. The bradykinin family is distinct from the tachykinin family of peptides, though both have profound hypotensive actions and contract many intestinal and other smooth muscles. Historically, it was noted that the former action was relatively slow-developing, hence the name bradykinin. Notable actions of bradykinin and kallidin are to dilate blood vessels and increase their permeability to plasma proteins, and to stimulate sensory nerve C-fibres. These actions are pro-inflammatory, and reflect the fact that the kinin-formation system is activated in inflammation, and enzymes (kallikreins) form the kinins from blood-borne or tissue precursors (kininogens) on injurious insult. 

Ungar, Damgaard and Weinstein have shown that certain well recognized anti-inflammatory drugs, salicylic acid, phenazone, amidopyrine, cinchophen and also jf)-aminophenol inhibit fibrinolysin (plasmin) in concentrations close to those which show anti-inflammatory activity in vivo. Salicylate may inhibit kinin formation by this indirect mechanism involving plasmin. The failure of some workers to observe any inhibition of kallikrein by salicylate in vitro does not conflict with this. 

Antagonism of Kinin Formation and Action We have seen above (page 62) that bradykinin may be the intermediate factor responsible for many of the manifestations of inflammation. It is natural to consider the possibility that anti-inflammatory drugs may inhibit either the formation or the action of bradykinin. 

Northover and Subramanian report that formation of kinin by serum and salivary kallikrein is inhibited by sodium salicylate, acetylsalicylic acid, phenylbutazone and certain other anti-inflammatory substances. The vasodepressor and vascular permeability activities of kallikrein are similarly inhibited. These findings are not, however, supported by investigations of other workers and further studies are needed to clarify the discrepancy. It is interesting to note that hexadimethrine bromide(polybrene), which is known to inhibit kinin formation in vitro, inhibits increased capillary permeability in the xylene treated skin of mice . 

Rheumatoid factor may be the immunological link between white blood cells and the body s defense systems Generated 22 S antigen-antibody complex can activate asma kallikrein and lead to kinin formation and subsequent synovitis. ... 

Figure 2. Mechanism of kinin formation by kallikrein and other kinin releasing enzymes.

The questions that we are led to ask are, how does this system produce the kinins and how can we estimate the extent of kinin formation ... 

Although these artefacts could make important differences to the small amounts of kinins usually observed, the amounts of enzyme or substrate used up would not significantly affect their assay. The answer to the question of how to estimate the extent of kinin formation at a site of injury would therefore be to examine the enzyme and substrate concentrations rather than those of the peptides themselves. 

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