Kinins and neuroinflammation: dual effect on prostaglandin synthesis

The role of kinins, well known as peripheral inflammatory mediators, in the modulation of brain inflammation is unclear. The present data show that bradykinin, a bradykinin B(2) receptor agonist, enhanced both basal and lipopolysaccharide-induced prostaglandin E(2) synthesis in rat neonatal glial cells in culture. By contrast, Lys-des-Arg(9)-bradykinin, which is a kinin breakdown product and a selective bradykinin B(1) receptor agonist, attenuated both basal and lipopolysaccharide-induced production of prostaglandin E(2) in glia. These results suggest a feedback regulatory mechanism of kinins on glial cells, in which prostaglandin synthesis is initially enhanced by bradykinin (B(2)) and eventually blocked by the effect of the kinin breakdown product, acting on bradykinin B(1) receptors.