Kinins

Kinins are a family of small peptide mediators involved in inflammation, pain, and cardiovascular regulation. Bradykinin is the best-known kinin, with kallidin (lys-bradykinin) and related peptides also active. They are generated from kininogens by the kallikrein–kinin system.

Kininogens are plasma glycoproteins produced mainly by the liver. Plasma kallikrein cleaves high-molecular-weight kininogen to bradykinin, while tissue kallikrein cleaves low-molecular-weight kininogen to kallidin, which can be converted to bradykinin by aminopeptidases. The contact system, involving factor XII and prekallikrein, can activate kallikrein upon contact with negatively charged surfaces. Kinins are rapidly inactivated by kininases, including kininase II (angiotensin-converting enzyme) and various aminopeptidases, giving them a short half-life.

Kinins exert most effects through kinin receptors. Bradykinin and kallidin bind primarily to the B2 receptor, which is constitutively expressed; B1 receptors are inducible during inflammation and respond to des-Arg9-bradykinin. Receptor activation promotes vasodilation via nitric oxide and prostacyclin, increases vascular permeability leading to edema, and directly stimulates sensory nerves to produce pain. Bronchoconstriction and smooth muscle effects can also occur in certain contexts.

Clinical relevance includes disorders tied to excessive kinins. Hereditary angioedema, often due to deficiency of C1 esterase inhibitor, involves excessive bradykinin and swelling. Angioedema can also be a side effect of ACE inhibitors, which raise bradykinin levels. Therapies targeting the kallikrein–kinin system—such as B2 receptor antagonists (e.g., icatibant), kallikrein inhibitors (e.g., ecallantide), and C1 esterase inhibitors—are used in conditions like hereditary angioedema.