Localization of components of the kallikrein-kinin system in the kidney: relation to renal function. State of the art lecture.

The renal kallikrein-kinin system (KKS) is a complex multienzymatic system, the main components of which are the enzyme kallikrein, the substrate kininogen, effector hormones or kinins (lysyl-bradykinin, bradykinin), metabolizing enzymes (several kininases, the most relevant being kininases I and II [ACE] and neutral endopeptidase 24.11 [NEP]), and an as-yet unknown number of activators and inhibitors of kallikrein and kininases. The renal KKS seems to participate in both intrarenal and extrarenal complex events such as control of the extracellular volume, regulation of blood pressure, and control of sodium and water excretion, renal vascular resistance, and renin release. The biology of components of the KKS, including its regulation, molecular biology, and abnormalities associated with major diseases such as hypertension and diabetes mellitus, has been reviewed in recent years.With regard to the main components of the KKS, it is currently known that 1) kininogens are found in large amounts in the interstitial fluid and plasma, 2) kallikrein is rapidly inactivated by several protease inhibitors when released into the circulation, 3) kinins have short half-lives in plasma, being rapidly degraded by 4) several kininases ubiquitously found in endothelial cells, the brush border of proximal convoluted tubular cells, distal tubular cells, urine, and plasma. These considerations led others to hypothesize that the KKS functions in a paracrine fashion, regulating local tissue function near where the hormones are released. The purpose of this review is to address the cellular localization of some of the main components