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 B₂ receptor agonist, enhanced both basal and lipopolysaccharide-induced prostaglandin E₂ synthesis in rat neonatal glial cells in culture. By contrast, Lys-des-Arg⁹-bradykinin, which is a kinin breakdown product and a selective bradykinin B₁ receptor agonist, attenuated both basal and lipopolysaccharide-induced production of prostaglandin E₂ in glia. These results suggest a feedback regulatory mechanism of kinins on glial cells, in which prostaglandin synthesis is initially enhanced by bradykinin (B₂) and eventually blocked by the effect of the kinin breakdown product, acting on bradykinin B₁ receptors.