Kinine

Kinins are biologically active peptides (tissue hormones) that can trigger an inflammatory response. Kinins exert their biological activity by binding to their corresponding kinin receptors, which are expressed in the cell membrane of various cell types. active oligopeptides, which are tissue hormones. Important representatives include bradykinin and lys-bradykinin (kallidin). Kinins are formed under the action of the serine protease kallikrein from precursor substances, the kininogens.

A distinction is made between

• high molecular weight kininogen (HMWK) and
• low molecular weight kininogen (LMWK).

Both kininogens are produced by tissue-specific, alternative splicing from the kininogen gene and only differ in the C-terminal region. Kinins promote vasodilatation, vascular permeability, nociception and pain in loco (Marceau F et al. 2004).

Kinins develop their biological activities by binding to kinin receptors. So far, two kinin receptors belonging to the superfamily of G-protein-coupled receptors have been described:

• kinin receptor B1(B1R) and
• kinin receptor B2(B2R) (Leeb-Lundberg LMF et al. 2005).

The mRNAs for the kinin receptor genes have been detected in normal human skin and in biopsies from patients with various skin diseases (Dagnino et al. skin diseases (Dagnino APA et al. 2020). Versch. Studies have shown that the kinin B2R binding sites are concentrated in the stratum basale of the human epidermis, while immunohistochemistry revealed immunoreactivity for the receptor protein on the cell surface of keratinocytes throughout the epidermis (Vidal MA et al. 2005). These were also detected in epidemic cell cultures from normal human epidermis, as were the B1R and B2R proteins themselves.

The kinin B1 receptor is only expressed at low levels in normal tissues, but is rapidly upregulated by proinflammatory cytokines (e.g. by interleukin-1beta, interleukin-2, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma), cellular stress and inflammation. There are many indications that high concentrations of kinin peptides occur in both acute and chronic inflammatory processes, which means that kinin receptors could play an important role in inflammatory skin diseases.

Furthermore, the kinin-kallikrein system plays an important role in the control of many biological processes, such as:

• blood clotting
• blood pressure regulation
• pain

Versch. Models have shown that kinin B1R, the bradykinin-1 receptor protein, is an important modulator of chronic inflammation (Marceau F et al. 2004). Bradykinin and Lys-bradykinin (= kallidin, a decapeptide with the sequence H-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH) have a half-life of 15 to 30 seconds in plasma. This can be increased by the acidic pH value of the inflammatory environment. The carboxypeptidases N and M cleave the Phe8-Arg9 bond at the carboxy-terminal end of the bradykinin-2R agonists, bradykinin and Lys-bradykinin, to generate two new ligands: Lys-des[Arg9]bradykinin. This is a potent agonist of the human B1R, and [Arg9]bradykinin with greater affinity for the mouse receptor (Leeb-Lundberg LMF et al. 2005). Once the kinins bind to their receptors, they activate a number of intracellular signaling pathways, some of which apply to both B1R and B2R. These pathways include the mobilization of Ca2+ and the release of arachidonic acid.

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