[Significance of kallikrein-kinin system in central nervous system diseases]

Kallikreins cleave kininogens to release kinins. Kinins exert their biological effect by activating constitutive bradykinin receptor-2 (BR2) and inducible by inflammatory cytokines bradykinin receptor-1 (BR1). Studies in animal models and some clinical observations indicate tat the activation of kallikrein - kinin system may have relevance to central nervous system (CNS) diseases, including multiple sclerosis, Alzheimer's disease, epilepsy as well as cerebral ischemia and neoplasmatic tumors. The actions of kinins include vasodilatation and increased vascular permeability may contribute to blood-brain barrier disruption. Kinins evoke pain, and stimulate of endothelial cells, white blood cells, astrocytes and microgia cells to release of prostanoids, cytokines, free radicals, nitric oxide. Kinins stimulate angiogenesis and proliferation of tumor cells. These events lead to neural tissue damage and long lasting disturbances in blood-brain barrier function. In animal models the overexpression of genes and proteins of tissue kallikrens, kininogen as well as RB1 and RB2 has been observed. Kinin receptors antagonists, especially B1R blockade decreased morphological and biochemical features of CNS inflammation. On the other hand in brain tumor models RB1 and RB2 activation has been shown to mediate reversible blood-brain barrier permeability to enhance anti-cancer drug delivery, which may have therapeutic potential.