The Kinin System: Present and Future Pharmacological Targets

Abstract

Kallikrein kinin system (KKS) is a complex system produced in various organs. This system includes kininogen (precursor for kinin), kallikreins and the pharmacologically active bradykinin (BK) which is considered either proinflammatory or cardioprotective. It's a proinflammatory polypeptide that is involved in many pathological conditions and can cause pain, inflammation, increased vascular permeability, vasodilation, contraction of various smooth muscle as well as cell proliferation. On the other hand, it has been shown that BK has cardioprotective effects as all components of KKS are located in the cardiac muscles. Numerous observations obtained show that decreased activity of this system may lead to cardiovascular diseases such as hypertension, cardiac failure and myocardial infarction. BK acts on two receptors, B 1 and B 2 receptors which are linked physiologically through their natural stimuli and their common participation in a variety of inflammatory responses. Recently, numerous BK antagonists have been developed in order to treat several diseases which are due to excessive BK formation. Although BK has many beneficial effects, some undesirable effects have been recognized that can be reversed with BK antagonists. In addition, products of this system have multiple interactions with other important metabolic pathways such as the renin-angiotensin system.

An Outline of Renal Artery Stenosis Pathophysiology—A Narrative Review

“…Taking into account the premises relating to the physiological and pathophysiological role of KKS, the numerous possibilities of pharmacological intervention based on the interference in the KKS (e.g., in the treatment of inflammation, sepsis, allergic reactions, hereditary angioedema, pulmonary embolism or acute respiratory distress syndrome) are being investigated [ 57 , 58 , 59 ]. Further detailed information on the organisation, physiology and pathophysiology, as well as the potential therapeutic approach of the KKS system, can be found in numerous reviews [ 60 , 61 , 62 , 63 ]. Due to the significant vasodilatory effect produced by BK, conditioned by its own action and potentiated by the secondary release of other vasoactive autacoids, such as eicosanoids, nitric oxide, endothelium-derived hyperpolarising factor and tissue plasminogen activator, KKS play an important role in the regulation of cardiovascular and renal functions.…”

Pharmacological and Immunological Properties of Wasp Venom

“…They are important mediators of inflammatory responses, potent pain producers and increase vascular permeability and vasodilatation. [33,37,38] Bradykinin is a nonapeptide usually found in body secretions such as urine, saliva and sweat. They are also found in several tissues such as heart, vasculature, blood, kidney, colon and liver.…”

Kinin-generating cellular model obtained from human glioblastoma cell line U-373.

“…Such a difference in the expression of kinin receptors caused by pro-inflammatory cytokines may prove relevant to studies related to cancer treatment with antagonists that have gained in importance in recent years (Sharma & Al-Sherif, 2011;Figueroa et al, 2012).…”