Kallikreins physiology

Kallikreins are present in plasma and in several tissues, including the kidneys, pancreas, intestine, sweat glands, and salivary glands. Plasma prekallikrein can be activated to kallikrein by trypsin, Hageman factor, and possibly kallikrein itself. In general, the biochemical properties of tissue kallikreins are different from those of plasma kallikreins. Kallikreins can convert prorenin to active renin, but the physiologic significance of this action has not been established. 

In general, the examination of sequence variation within the 300-kb kalli-krein locus has not been performed in detail, and it is therefore possible that inactivating mutations within the coding region of kallikrein genes exist but await discovery. Kallikrein gene inactivation in human diseases would likely provide clues for the physiological functions of these diseases. 

Another possible mechanism for kallikrein action in physiology and pathobiology is the activation of proteinase-activated receptors (PARs). PAR is a recently described family of G-protein-coupled receptors with seven transmembrane domains that are stimulated by cleavage of their N-termini by a serine protease rather than by ligand-receptor interaction [184-186]. Four PARs have been identified so far, of which PARI, PAR3,... 

Margolius HS. Tissue kallikreins Structure, regulation, and participation in mammalian physiology and disease. Clin Rev Allergy Immunol 1998 16 337-349. 

Activation of factor XII leads to complex events (30) connecting several areas of physiology. Interfaces accidentally introduced are sometimes ignored. For example, the surface of bacteria may activate factor XII (31) and thus be responsible for the finding that immune complex activates factor XII directly. There is the lack of strict specificity in the actions of several enzymes. For example, factor XII is needed for the conversion of prekallikrein (perhaps identical with Fletcher factor) to kallikrein by glass (32). Then conversion of kininogen to kinin by kalli-krein follows but several precursors may activate themselves as well as others (33). 

Direct pDNA transfer technique had been used to examine the role of a physiologically related protein transduction signal pathway toward certain endogenous disease phenotype, such as investigating the function of the tissue kallikrein-kinin system (KKS) in the central control of blood pressure homeostasis... 

FIGURE 30-5 Modified from Jackson EK et al. Physiological functions of die renal prostaglandin, renin, and kallikrein systems. In The Kidney Physiology and Pathophysiology. DW Seldin and G Giebisch (eds). New York, Raven, 1985. 

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 renal kallikrein-kinin [40] system has been suggested as influencing renal hemodynamic as well as excretory function. This activity may also be linked to arachidonate metabolites, like PGEj, since increased excretion of cyclooxygenase products are associated with increased kallikrein-kinin excretion. However, the physiological significance of this relationship is uncertain. 

Schmaier AH. The contact activation and kallikrein/kinin systems pathophysiologic and physiologic activities. J Thromb Haemost 2016 14 28-39. 

Colman R. Contact activation (kallikrein-kinin) pathway multiple physiologic and pathophysiologic activities. Philadelphia Lippincott WilUams Wilkins 2006. 

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