Regulation, of kallikreins

Recently, Palmer et al., working with human colon cancer cell lines, reported dramatic up-regulation of kallikreins 6 and 10 by la, 25-dihydroxyvitamin D3 [158]. This finding raises the possibility that some kallikreins could be regulated by a multitude of nuclear receptors. 

Cl-Inh belongs to a superfamily of serine protease inhibitors (serpins) and is a major inhibitor of F-XIIa and kallikrein. It is also an inhibitor of activated complement factors C1 q, C1 r, and C1 s. C1 -Inh thus regulates the activation of two important plasma cascade systems. Proteases induce a conformational change in the plasma protein a2-M, which results in entrapment of the protease into the a2-M cage (B4). In vivo, a2-M acts as a second inhibitor of kallikrein. 

Murray SR, Chao J, Lin FK, Chao L. Kallikrein multigene families and the regulation of their expression. J Cardiovasc Pharmacol 1990 15 S7-S16. 

Gerald WL, Chao J, Chao L. Sex dimorphism and hormonal regulation of rat tissue kallikrein mRNA. Biochim Biophys Acta 1986 867 16-23. 

Yousef GM, Scorilas A, Chang A, et al. Down-regulation of the human kallikrein gene 5 (KLK5) in prostate cancer tissues. Prostate 2002 51 126-132. 

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],... 

Bradykinin 87 and kallidin (Lys-bradykinin-decapeptide), which are split off from the kininogen in the plasma by trypsin and kallikrein respectively (Fig. 10), hardly differ in their pharmacological activity. The most important effect of the kinins is a dilation of the peripheral vessels, which leads to an improved blood flow, in the kidneys for example, and therefore increases diuresis. By acting on the formation of angiotensin II, kinins can contribute to the regulation of blood pressure. Moreover, kinins cause a contraction of the bronchial muscle. 

CARDIOVASCULAR SYSTEM Bradykinin causes vasodilation by activating its B receptor on endothelial cells. The endotheUum-dependent dilation is mediated by NO, prostacyclin, and a hyperpolarizing epoxyeicosatrienoic acid that is a CYP-derived metabolite of arachidonic acid. The endogenous kallikrein-kinin system plays a minor role in the regulation of blood pressure under normal circumstances, but it may be important in hypertensive states. 

KInIns, human peptide hormones implicated in many physiological and pathological processes, including reduction of blood pressure and regulation of sodium homeostasis, inflammation and the cardioprotective effects of preconditioning. The kallikrein-kinin system (KKS) of the plasma generates bradykinin (BK), whereas the tissue KKS is responsible for the formation of kallidin. The kinin action is mediated via two types of kinin receptor, the type 1 (Bi) and type 2 (B2). Bi... 

The kallikrein-kinin system as a regulator of cardiovascular and renal function, in Hypertension, Pathophysiology, Diagnosis and Management, 2nd edn (eds J.H. Laragh and B.M. Breimer), Raven Press Ltd., New York, NY, pp. 983-999. 

Kallidin-Klnin System - Recent work has also suggested a role for the kallidin-kinin system in the pathogenesis of hypertensiotiP . Significant increases in urinary excretion of kallikrein were found in spontaneously hypertensive and DOCA-salt hypertensive rats, while levels found in rats with renal hypertension and patients with essential hypertension were lower than those in respective controls. Additional data suggests that the kallidin-kinin system may be intimately involved in the regulation of salt and water excretion by the kidney . ... 

Inhibitors that block the protease activity of F-XIIa and kallikrein. Plasma contains two protease inhibitors that regulate contact activation Cl inhibitor (Cl-Inh) and a2-macroglobulin (a2-M). 

Comparison of the IE patterns of a few studied kallikreins in different tissues revealed no major differences, indicating that they may share a common mode of regulation. It is worth mentioning that our results concerning the IE of the studied hKs in different normal human tissues correspond fairly... 

Promoter analysis and hormonal stimulation experiments allowed us to obtain insights into the mechanisms that regulate expression of the human kallikrein genes. In addition to KLK3 and KLK2, and more recently KLK10, no other kallikrein gene promoter has been functionally tested. 

Steroid hormones, acting through their receptors, play important roles in the normal development and function of many organs. In addition, they are involved in the pathogenesis of many types of cancer [146], Several reports confirmed that many kallikreins are under steroid hormone regulation in endocrine-related tissues and cell lines [100, 147-155],... 

---