The role of the kallikrein-kinin system in joint inflammatory disease.
Components of kallikrein-kininogen-kinin are activated in response to noxious stimuli (chemical, physical or bacterial), which may lead to excessive release of kinins in the synovial joints that may produce inflammatory joint disease. The inflammatory changes observed in synovial tissue may be due to activation of B2 receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor antagonists may provide valuable new analgesic drugs. The mode of excessive kinin release in inflamed synovial joints leads to stimulation of pro-inflammatory actions of B2 kinin receptors. These properties could be antagonized by novel B2 receptor antagonists (see Fig. 4). Further, it is suggested that substances directed to reduce the activation of KKS may provide a pharmacological basis for the synthesis of novel antirheumatic or anti-inflammatory drugs.
Sharma
J N
JN
Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan.
D000818:Animals; D000893:Anti-Inflammatory Agents; D001168:Arthritis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology*; D005463:Fluoroacetates; D006801:Humans; D007596:Joints / Q000378:metabolism; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007704:Kininogens / Q000378:metabolism; D007705:Kinins / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D011453:Prostaglandins / Q000096:biosynthesis; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002867:Chromones; D005463:Fluoroacetates; D007704:Kininogens; D007705:Kinins; D015289:Leukotrienes; D009842:Oligopeptides; D011453:Prostaglandins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C069620:B 3824; C069621:RC 39II