Kininogen I Activators

High Molecular Weight Kininogen (HMWK) Activators encompass a range of chemical compounds that indirectly augment the functional activity of HMWK through various signaling pathways. Bradykinin, the primary peptide cleaved from HMWK, significantly influences vascular permeability and pain when bound to its B1 and B2 receptors, indirectly enhancing HMWK's role due to the autocrine and paracrine signaling involved. Similarly, Kallikrein, a serine protease, directly cleaves HMWK to release bradykinin, thus directly activating HMWK's function in physiological processes such as vasodilation and pain sensation. Heparin enhances HMWK's susceptibility to kallikrein cleavage, facilitating bradykinin release, while Thrombin, through the coagulation cascade, contributes to the generation of bradykinin by cleaving HMWK. Factor XII (Hageman factor) acts as an initiatorof the intrinsic coagulation cascade, where HMWK serves as an essential cofactor, and its activation by Factor XII leads to a downstream enhancement of HMWK's coagulation-related functions. Prekallikrein, another component of the kallikrein-kinin system, when activated to kallikrein, also targets HMWK to produce bradykinin, underpinning the importance of HMWK in inflammation and coagulation processes.

Metal ions such as Zinc and Copper modulate the activity of proteases that cleave HMWK, indirectly influencing the functional pathways in which HMWK is involved. The regulatory role of C1-Inhibitor over proteases that activate HMWK highlights the intricate control mechanisms governing the kallikrein-kinin system. Dextran Sulfate promotes the activation of Factor XII, which in turn enhances HMWK activity, reflecting the interconnectedness of coagulation and inflammatory pathways. Dimethyl Sulfoxide (DMSO) has been observed to foster the cleavage of HMWK to bradykinin, thus supporting HMWK's role in mediating inflammatory responses. Lastly, Phospholipids provide the necessary platform for coagulation factor assembly and HMWK activation, delineating their contribution to the intrinsic pathway of coagulation and the subsequent generation of bradykinin, a key mediator of HMWK's biological activities.