Expression and function of bradykinin receptors in microglia

Release of Bradykinin and Expression of Kinin B2 Receptors in the Brain: Role for Cell Death and Brain Edema Formation After Focal Cerebral Ischemia in Mice

“…Expression of the bradykinin B 2 receptor has been reported on cultured astrocytes, oligodendrocytes, and microglia (Cholewinski et al, 1991;Gimpl et al, 1992;Stephens et al, 1993;Hosli and Hosli, 1993;Noda et al, 2003), and functional studies in vitro and in vivo suggest the presence of the B 2 receptor on cerebral endothelial cells (Whalley and Wahl, 1983;Wahl et al, 1983;; however, in the brain, constitutive expression of bradykinin B 2 receptors has only been reported in neurons (Raidoo et al, 1996;Chen et al, 2000), as also confirmed by our own results (Figures 2 and 4). Neuronal B 2 receptor expression has been detected in most areas of the brain, including in the regions of the brain affected by MCAO, that is, the cerebral cortex and the striatum (Raidoo et al, 1996;Chen et al, 2000) ( Figure 4).…”

“…Bradykinin might be involved in neuronal signalling by causing calcium-dependent release of glutamate from astrocytes (Parpura et al, 1994), induces the production of inflammatory mediators in glial cells (Schwaninger et al, 1999), and increases intracellular calcium in microglial cells (Noda et al, 2003). Data on the expression of kininogen mRNA in cultured neurons and astrocytes and immunohistological studies on brain sections indicated that bradykinin was found only in neurons (Correa et al, 1979;Takano et al, 1999); however, the precise source of bradykinin production in the CNS is still unknown.…”

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

“…Activation of both receptors promotes intracellular calcium mobilization by inositol 1,4,5-triphosphate, production by phospholipase C-beta activity, and evoke release of nitric oxide and prostaglandins (Marceau and Regoli, 2004;Thornton et al, 2010). Both receptor subtypes are expressed by many cell types, including neurons (Couture et al, 2001), glial cells (Gimpl et al, 1992;Stephens et al, 1993;Noda et al, 2003), endothelial cells (Miyamoto et al, 1999) and vascular smooth muscle cells (Yang et al, 1999). In the human brain, components of KKS were found specifically in the thalamus, hypothalamus, cerebral cortex and spinal cord (Raidoo and Bhoola, 1997).…”

“…An in vitro study primary microglia showed that resting microglial cells did not express the B1BKR, while the B2BKR was constantly expressed. The addition of BK to the microglia culture induced B1BKR expression, while B2BKR expression was up to 50% down regulated (Noda et al, 2003(Noda et al, , 2004. During inflammation, BK is neuroprotective by up-regulating expression rates of kinin receptor, which are responsible for reducing microglia-induced proinflammatory responses in the presence of lipopolysaccharide (LPS), leading to inhibition of TNF-α and IL-1β expression (Noda et al, 2007b).…”

“…The resulting inflammation would induce the production of BK and its degradation into DBK, which activates B1BKR expressed in microglial cells, promoting further increase in B1BKR expression (Noda et al, 2003). At the same time, the constitutively expressed B2BKR receptor would be down-regulated in presence of BK (Noda et al, 2007a), leading to constant activation of GSK-3β and TNF-α expression.…”