Kallidin, also known as lysyl-bradykinin, is a kinin peptide that plays a significant role in various physiological and pathological processes. It is a product of the kallikrein-kinin system, which is involved in inflammation, blood pressure regulation, pain, and other critical functions. Kallidin exerts its effects by interacting with specific cell surface receptors, primarily the bradykinin B2 receptor, leading to a cascade of biological responses1568.
In asthmatic subjects, kallidin has been shown to provoke potent bronchoconstriction when inhaled, suggesting a role in the pathogenesis of bronchial asthma. This effect is thought to be mediated by the B2 receptors, as evidenced by cross-tachyphylactic studies demonstrating reduced airway response to kallidin following exposure to bradykinin1.
Kallidinogenase, an enzyme that produces kallidin, has been studied for its neuroprotective effects in cerebral ischemia. In a mouse model of middle cerebral artery occlusion, human urinary kallidinogenase (HUK) treatment resulted in improved neurological function, reduced infarct size, and suppressed inflammation. The mechanism involves the inhibition of the nuclear factor-kappa B (NF-κB) pathway and activation of the MAPK/ERK pathway, highlighting the potential therapeutic application of kallidinogenase in stroke2.
In the context of retinal vein occlusion (RVO), kallidinogenase has been used to reduce retinal edema and the size of non-perfused areas. The treatment increases blood flow and promotes the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), suggesting an Akt/eNOS-dependent mechanism. These findings support the use of kallidinogenase as a therapeutic agent for RVO patients3.
Kallidin, along with bradykinin, has been found to increase myocardial blood flow and reduce myocardial vascular resistance. This vasodilatory effect is dose-dependent and demonstrates the sensitivity of the myocardial vascular bed to kallidin. However, in contrast to bradykinin, kallidin does not seem to stimulate metabolic heat production in the myocardium, indicating a difference in their effects on myocardial metabolism4.
The role of kallidin in skin inflammation has been explored in both normal and psoriatic subjects. Intradermal injections of kallidin induce weal and flare responses, which are key features of inflammation. The comparison of these responses between normal individuals and patients with psoriasis could provide insights into the involvement of kinins in psoriatic pathology7.
The kallikrein-kinin system, of which kallidin is a part, is known to be intimately involved in renal function. Kallidin acts as a potent stimulus for renal biochemical and physiological events, and abnormalities in the system have been associated with renal pathologies. The system's sensitivity to drugs affecting renal function further underscores its significance in renal physiology6.
Kallidin mediates its effects through the activation of the bradykinin B2 receptor, which is a G protein-coupled receptor. Upon binding to this receptor, kallidin triggers a series of intracellular signaling pathways, including the phosphoinositide pathway, leading to the production of inositol phosphates and diacylglycerol. This results in the release of calcium from intracellular stores and the activation of protein kinase C (PKC). The activation of these signaling pathways can lead to various physiological responses, such as vasodilation, increased vascular permeability, and stimulation of inflammatory mediators58.
Interestingly, kallidin can also be directly activated by serine proteases such as kallikreins, which suggests a unique mechanism of receptor activation that is independent of its release from kininogens. This direct activation does not involve cross-desensitization with bradykinin, indicating a distinct pathway of action8.
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