Inflammation kinins

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... 

At the cellular level, eosinophils, mast cells, alveolar macrophages, lymphocytes and neutrophils recruited to the airways of asthmatics produce a variety of inflammatory mediators, such as histamine, kinins, neuropeptides, and leukotrienes, which lead to airway smooth muscle constriction and obstruction of airflow, and the perpetuation of airway inflammation [20, 21]. An understanding of the inflammatory processes and the molecular pathways of these mediators has led to the development and widespread use of several pharmacologic agents that mitigate airway inflammation and bronchoconstriction. 

Vasoactive substances (histamine, kinins, prostaglandins) are released at sites of inflammation, increasing blood flow and vascular permeability. This causes edema, warmth, erythema, and pain and makes it easier for granulocytes to pass from blood vessels to sites of inflammation. 

Other actions of kinins include activation of clotting factors simultaneously with the production of bradykinin. In the kidney, bradykinin production results in an increase in renal papillary blood flow, with a secondary inhibition of sodium reabsorption in the distal tubule. In the peripheral nervous system, bradykinin is important for the initiation of pain signals. It is also associated with the edema, erythema, and fever of inflammation. 

In addition to the phagocytic activity of the leukocytes, small peptide substances, such as the kinins, which are thought to be partially responsible for the local inflammatory response in gouty arthritis, accumulate in the joint space. The inflammation is associated with local vasodilation, increased vascular permeability, and pain. 

Bradykinin has long been known to produce the four classic symptoms of inflammation—redness, local heat, swelling, and pain. Kinins are rapidly generated after tissue injury and play a pivotal role in the development and maintenance of these inflammatory processes. 

Icatibant Selective antagonist of kinin B2 receptors Blocks effects of kinins on pain, hyperalgesia, and inflammation Potential use for inflammatory pain and inflammation... 

Icatibant is a second generation B2 receptor antagonist. It is orally active, potent, and selective, has a long duration of action (> 60 minutes), and displays high B2 receptor affinity in humans and all other species in which it has been tested. Icatibant has been used extensively in animal studies to block exogenous and endogenous bradykinin and in human studies to evaluate the role of kinins in pain, hyperalgesia, and inflammation. 

Clements J. The molecular biology of the kallikreins and their roles in inflammation. In Farmer S, editor. The Kinin System. New York Academic Press, 1997 71-97. 

Bhoola K, Ramsaroop R, Plendl J, Cassim B, Dlamini Z, Naicker S. Kallikrein and kinin receptor expression in inflammation and cancer. Biol Chem 2001 382 77-89. 

Muscle cells release kallikrein during inflammation causing formation of active kinin peptides (bradykinin and kallidin) from kininogen [65, 66]. Kinins are peptide hormones that produce vasodilation, increase capillary permeability, and cause pain and infiltration of neutrophils. There is a direct correlation between the amount of kinin in plasma or tissues and the degree of inflammation. Vascular dilation causes increased blood flow to infection [67, 68], Bik inhibits formation of kinins and vascular dilation by kallikrein, thereby inhibiting smooth muscle contraction [69-71],... 

Inflammation leads to vasodilation that damages the endothelial and epithelial layers, thus promoting vascular disease [4], Kallikrein, neutrophil elastase, and mast cell tryptase release kinins from kininogens. Kinins are... 

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],... 

Kaplan A, Silverberg M, Dunn J, Ghebrehiwet B. Interaction of the clotting, kinin forming, complement, and fibrinolytic pathways in inflammation. Ann NY Acad Sci 1982 389 25-38. 

Bradykinin and related kinin peptides are produced by leucocytes and act via Gaq to elevate cytosolic Ca2+ and promote nitric oxide (NO) synthesis, smooth muscle contraction, capillary permeability, inflammation and histamine release from mast cells. 

A protein which circulates inactively, until activated by collagen, platelets or exposed basement membranes via conformational change. When activated, it in turn is able to activate three plasma systems involved in inflammation the kinin system, fibrinolysis system and coagulation system. 

The kinin-kallikrein system (kinin system) is a poorly delineated system of blood proteins that plays a role in inflammation, blood-pressure control, coagulation and pain. Kinins are small peptides produced from kininogen by kallikrein, which are subsequently degraded by kininases. They act on phospholipase and increase arachidonic acid release and thus prostaglandin (PGE2) production. 

Couture R, Harrisson M, Vianna RM, Cloutier F (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol 429 161-176... 

Bradykinin is a vasoactive nonapeptide which is the most important mediator generated by the kinin system and it is involved in inflammation processes (Calixto et al, 2000). Kinins so far identified include bradykinin and kallidin. They cause local increases in the permeability of small blood vessels. Bradykinin is a potent stimulator of pain receptors in the skin and has a powerful influence on stimulating smooth muscle contraction, inducing hypotension, and increasing blood flow and permeability of capillaries Cyvetal, 2001). 

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