Kinin system

Blais Jr, Marceau F, Rouleau JL et al (2000) The kallikrein-kininogen-kinin system lessons from the quantification of endogenous kinins. Peptides 21 1903—1940... 

Pixley RA, Colman RW (1997) The kallikrein-kinin system in sepsis syndrome. In Farmer SG (ed) Handbook of immunopharmacology - the kinin system. Academic Press, New York, pp 173-186... 

Bradykinin is part of the kallikrein-kinin system, which shares a link to the RAAS through angiotensin-converting enzyme. Bradykinin is a vasodilatory peptide that is released in response to a variety of stimuli, including neurohormonal and inflammatory mediators known to be activated in HF.9 As a... 

It was hoped that the more complete blockade of angiotensin II s AT effects would confer greater long-term efficacy with ARBs compared to ACE inhibitors. However, prospective, randomized trials suggest that the clinical efficacy of ARBs is similar to that of ACE inhibitors for reduction of hospitalizations for HF, sudden cardiac death, and all cause mortality.23-25 Despite poorer suppression of AT2, comparable efficacy of ACE inhibitors may be due to the additional effects on the kallikrein-kinin system. Although ARBs produce hemodynamic and neurohormonal effects similar to those of ACE inhibitors, they are considered second-line therapy due to the overwhelming clinical trial experience with ACE inhibitors. 

D9. DeLa Cadena, R. A., Suffredini, A. F Kaufman, N., Parrillo, J. E., and Colman, R. W., Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers. Blood 81,3313-3317(1993). 

Limited data on occupationally exposed men indicate that the effect of lead on blood pressure may be mediated in part through the renin-angiotensin system, as evidenced by lead-related increases in plasma renin and angiotensin I levels (Campbell et al. 1985) and the kallikrein-kinin system, as indicated by a correlation between renin and kallikrein (Boscolo et al. 1981). Evidence from patients with essential hypertension and renal impairment suggests that excessive lead absorption may be involved in the development of both conditions (Batuman et al. 1983). 

The kallikrein-kinin system is an enzymatic pathway giving rise to two predominant vasoactive peptides, kallidin and bradykinin. Kallikrein, the enzyme responsible for the formation of these peptides, exists in plasma and tissues. However, circulating levels of the end products, kalhdin and bradykinin, are quite low because the kalhkrein enzymes are present largely in inactive forms. In addition, the short half-life of these peptides (15 seconds) also contributes to low plasma levels. In general, the kinins produce relaxation of vascular smooth muscle and vasodilation. Bradykinin causes... 

Kinins are potent vasodilator peptides formed enzymatically by the action of enzymes known as kallikreins or kininogenases acting on protein substrates called kininogens. The kallikrein-kinin system has several features in common with the renin-angiotensin system. 

The kallikrein-kinin system. Kininase II is identical to converting enzyme peptidyl dipeptidase (ACE). 

Drugs that modify the activity of the kallikrein-kinin system are available, though none are in wide clinical use. Considerable effort has been directed toward developing kinin receptor antagonists, since such drugs have considerable therapeutic potential as anti-inflammatory and antinociceptive agents. Competitive antagonists of both and B2 receptors are available for research use. Examples of B receptor... 

Costa-Neto CM et al Participation of kallikrein-kinin system in different pathologies. Int Immunopharmacol 2008 8 135. [PMID 18182216]... 

Overall, the kinins are an important part of a well-organized physiological system. The various aspects and interdependencies of the kinin system have been, and continue to be, the focus of intensive research efforts in many laboratories. Many pharmaceutical companies have identified this system as an ideal site for therapeutic intervention in many inflammatory diseases. Hence, there have been many diverse approaches taken toward the discovery of antagonists (peptide and nonpeptide) of B2 and B1 receptors. This review focuses on the structure-based design strategies pursued in our laboratories during the past several years. 

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. 

Sharma JN, Uma K, Noor AR, Rahman AR. Blood pressure regulation by the kallikrein-kinin system. Gen Pharmacol 1996 27 55-63. 

Campbell DJ. Towards understanding the kallikrein-kinin system Insights from measurement of kinin peptides. Braz J Med Biol Res 2000 33 665-677. 

Campbell DJ. The kallikrein-kinin system in humans. Clin Exp Pharmacol Physiol 2001 28 1060-1065. 

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. 

Bradykinin is an endogenous inflammatory substance that increases vascular permeability and produces tissue edema. The kallikrein-kinin system is very rapidly activated following brain injury resulting in the activation of kallikrein that cleaves kininogen to produce bradykinin. The effects of bradykinin are mediated by two different receptors B1 and B2. Very low levels of B1 are found under normal conditions. In contrast, the B2 receptor is constitutively expressed in a wide variety of tissues including the brain and mediates the majority of bradykinin effects (Couture et al., 2001). 

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). 

---