Cyclooxygenase activity in bradykinin-induced dermal extravasation. A study in mice and humans

ConclusionThese data suggest that COX activity contributes to bradykinin-induced dermal extravasation in mice and humans. In addition, our findings may open new treatment options and point to a potential activity of drugs interfering with the release of the COX substrate arachidonic acid, e.g. glucocorticoids.Graphical abstractGraphical illustration of the potential role of prostaglandin formation for dermal extravasation induced by activation of bradykinin type 2 receptors (B2). B2 translates the bradykinin signal via the Gq transduction pathway including generation of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) resulting in an increase of the intracellular concentration of Ca2+. This ion binds and activates a variety of intracellular proteins. Among those, binding to calmodulin is an essential step to activate endothelial NO synthase (eNOS), while binding to phospholipase A2 (PLA2) directly stimulates this enzyme to release arachidonic acid (AA) from the cell membrane and initiates the generation of PGH2 by cyclooxygenases (COX). This prostaglandin functions as a substrate for a variety of prostaglandin synthases (PG-S) finally resulting in formation of specific prostaglandins. Once synthetized, these lipid mediators are released by the producing endothelial cell into small dermal blood vessel and activate their receptors located either in the producing cell (autocrine), or in adjacent cells (paracrine) or both. This activation of endothelial prostaglandin r...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research