Bradykinin Receptors

Bradykinin is a proinflammatory and algesic mediator that can act via two types of receptor, B1 and B2 (56). While the acute effects of bradykinin are mediated by B2 receptors, B1 receptors come into play in chronic inflammatory processes and persistent hyperalgesia. There is experimental evidence that bradykinin contributes to visceral pain, given that intraperitoneal bradykinin gives rise to abdominal constriction responses (57) and to cardiovascular and gastric reflex responses (58). These reactions are brought about by the activation of B2 receptors and most likely related to the kinin's ability to stimulate serosal afferents from the intestine (53,59). The bradykinin B2 receptor-mediated excitation of afferent nerve fibers in the mesentery is augmented by PGE2, adenosine, and histamine (53,60), while, vice versa, bradykinin can enhance the activity of TRPV1 (61,62). The potential of bradykinin receptor blockade in visceral hyperalgesia (63) is borne out by a number of experimental studies. For instance, genetic knockout of neutral endopeptidase, an enzyme that cleaves bradykinin, leads to peritoneal hyperalgesia that is reduced by the B2 receptor antagonist icatibant (64). Icatibant likewise counteracts the inflammation-induced increase in the abdominal constriction response to colorectal distension and intraperitoneal acetic acid (65). In a model of nematode-induced intestinal infection, it has been shown that both B1 and B2 receptor antagonists can attenuate the postinfection hypersensitivity to jejunal distension (66). Interstitial cystitis is associated with enhanced levels of bradykinin in the urine (67), and experimental cystitis leads to upregulation of B;l and B2 receptors in the urothelium (68). A role of bradykinin in the pathophysiology of cystitis can be concluded from the findings that the hyperreflexia of the detrusor muscle caused by experimental cystitis is reduced by both Bj and B2 receptor antagonists, Bj receptor antagonists having an effect only after inflammation has set in (68-70).

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