Kallikrein and kinin receptor genes

Mahabeer, Rajeshree; Bhoola, K. D.

doi:10.1016/s0163-7258(00)00080-2

Cited by 55 publications

(44 citation statements)

References 137 publications

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“…This tissue serine protease is encoded by one of the kallikrein gene family, KLK1 gene, located on chromosome 19 locus q13.2 -q13.4 (41,42). Tissue kallikrein is widely distributed (kidney, blood vessels, central nervous system (CNS), pancreas, gut, salivary and sweat glands, spleen, adrenal, and neutrophils) (17,42), and this wide distribution suggests a paracrine function (43). The origin of tissue kallikrein detected in plasma has been suggested to be the exocrine glands.…”

Section: Tissue Kallikrein-kinin Systemmentioning

confidence: 99%

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The Kallikrein-Kinin System: Current and Future Pharmacological Targets

et al. 2005

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Abstract. The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). This complex system includes the precursors of kinins known as kininogens and mainly tissue and plasma kallikreins. The pharmacologically active kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.

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Section: Tissue Kallikrein-kinin Systemmentioning

confidence: 99%

“…Tissue kallikrein releases KD from LK (42), cleaving the Met 379 -Lys 380 and Arg 389 -Ser 390 bonds (45). Although LK is considered to be the main substrate of tissue kallikrein, tissue kallikrein is also capable of cleaving HK.…”

Section: Tissue Kallikrein-kinin Systemmentioning

confidence: 99%

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

et al. 2005

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“…Stimulation of G protein-coupled bradykinin receptors (BR), B1R and B2R, mediate the effects of bradykinin (BK), which include promotion of cell growth, proliferation and migration [1][2][3] . Further, TK activates matrix metalloproteinases (MMPs) involved in extra-cellular matrix (ECM) degradation 4,5 .…”

Section: Introductionmentioning

confidence: 99%

B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

Naidu¹,

Botha²,

Naidoo³

2014

Afr H. Sci.

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Background: The kallikrein-kinin system (KKS) is an endogenous pathway involved in angiogenesis and tumourigenesis, both vital for cancer growth and progression. Objectives: To investigate the effect of two bradykinin receptor (B1R and B2R) agonists on growth and motility of prostate tumour (DU145) and micro-vascular endothelial cells (dMVECs). Methods: Increasing concentrations of selective B1R and B2R agonists were added to cultured cells. Cell proliferation and migration were assessed using the 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and modified Boyden Chamber assays, respectively. Where significant stimulation was found, the influence of an antagonist was also investigated. Results: Neither growth nor motility of endothelial cells was affected by either agonist. In DU145 cells, while the B2R agonist was without any significant effect, the B1R agonist stimulated proliferation and migration at concentrations of 10nM and 50nM respectively. Further, this effect was abrogated when cells were pre-incubated with a B1R antagonist. Conclusions: Unlike the physiologically-active B2R, the pathologically-inducible B1R may be implicated in prostate tumourigenic events. The involvement of the KKS in malignant prostate pathology supports on-going exploration of bradykinin receptor antagonists as target candidates in the development of alternate approaches to cancer therapy.

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“…For instance, Streptococcus pneumoniae was not able to activate the contact system in this study. 8 BK and its metabolite desArg 9 BK are potent inflammatory mediators, causing hypotension, increased vascular permeability, edema formation, fever, and pain (for a review, see Mahabeer and Bhoola 9 ). Conversion of BK to desArg 9 BK involves the cleavage of a carboxy-terminal arginine by carboxypeptidases of the N and M type, also known as kininases type I.…”

Section: Introductionmentioning

confidence: 99%

“…8 BK and its metabolite desArg 9 BK are potent inflammatory mediators, causing hypotension, increased vascular permeability, edema formation, fever, and pain (for a review, see Mahabeer and Bhoola 9 ). Conversion of BK to desArg 9 BK involves the cleavage of a carboxy-terminal arginine by carboxypeptidases of the N and M type, also known as kininases type I. 10 There are 2 kinin receptors described in humans, B 1 receptor (B1R) and B 2 receptor (B2R) (for a review, see LeebLundberg et al 11 ).…”

Section: Introductionmentioning

confidence: 99%

Kinin receptor expression during Staphylococcus aureus infection

Bengtson

Phagoo

Norrby‐Teglund

et al. 2006

Blood

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An inappropriate host response to invading bacteria is a critical parameter that often aggravates the outcome of an infection. Staphylococcus aureus is a major human Gram-positive pathogen that causes a wide array of community-and hospital-acquired diseases ranging from superficial skin infections to severe conditions such as staphylococcal toxic shock. Here we find that S aureus induces inflammatory reactions by modulating the expression and response of the B1 and B2 receptors, respectively. This process is initiated by a chain of events, involving staphylococcal-induced cytokine release from monocytes, bacteriatriggered contact activation, and conversion of bradykinin to its metabolite IntroductionStaphylococcus aureus, an important opportunistic Gram-positive human pathogen, is the most common organism isolated from soft-tissue and wound infections. The bacterium can cause a variety of community-and hospital-acquired diseases ranging from relatively benign skin infections, such as furuncles and subcutaneous abscesses, to more severe conditions, including scaled skin syndrome, necrotizing pneumonia, endocarditis, sepsis, and staphylococcal toxic shock syndrome (for reviews, see Lowy 1 and Yarwood and Schlievert 2 ). In severe conditions, staphylococci may evoke an inappropriate inflammatory host response by modulating so-called host effector systems. For instance, S aureus produces a diverse range of virulence factors contributing to the inflammatory response, among others the enterotoxins and toxic shock syndrome toxin-1 (TSST-1) that form a class of substances also known as pyrogenic toxin superantigens or PTSAgs (for a review, see Balaban and Rasooly 3 ). PTSAgs can induce a profound inflammatory reaction by interacting with MHC class II molecules and T-cell antigen receptors disengaged from the normal antigen-specific signal transduction of T cells. 4,5 The resulting inflammatory response is by far greater than antigen-specific activation and leads to pathologic levels of proinflammatory cytokines. 6 The human contact system, also known as the kallikrein-kinin cascade or intrinsic pathway of coagulation, is another example of a system that can be targeted and affected during infection. 7 The contact system consists of 4 factors, 3 serine proteinases (coagulation factors XI and XII, and plasma kallikrein), and 1 nonenzymatic cofactor (high-molecular-weight kininogen). Normally, these factors circulate as zymogens in the bloodstream. Contact activation can occur for instance on newly exposed cellular surfaces and is regulated by limited proteolysis. The initial step is activation of coagulation factor XII, which converts plasma kallikrein into the active form. Active kallikrein in turn amplifies the activation of factor XII, eventually resulting in clot formation, and the release of bradykinin (BK) from the precursor molecule, high-molecularweight kininogen. Previous studies have shown an interaction between S aureus and the contact system leading to its activation at the bacterial surface. 8 As a result, B...

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Kallikrein and kinin receptor genes

Cited by 55 publications

References 137 publications

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

B1 but not B2 bradykinin receptor agonists promote DU145 prostate cancer cell proliferation and migration

Kinin receptor expression during Staphylococcus aureus infection

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