title: Differential effect of intranasally administrated kinin B1 and B2 receptor antagonists in Alzheimer's disease mice.
abstract: An Increasing body of evidence supports a critical role of brain inflammation in the pathogenesis of Alzheimer's disease. A principal aspect of the brain immune response to inflammation is the activation of microglia. It has been shown that the kinin system is activated during brain inflammation and previously we demonstrated that bradykinin B1 receptor agonist reduced microglial activation in vitro. The aim of the present study was to investigate the effects of bradykinin B1 or B2 receptor antagonists on microglial release of pro-inflammatory factors in BV2 microglia. In vivo, we focused on the effects of intranasally given kinin antagonists on amyloid burden and microglia/macrophage marker expression in brains of 5X familial Alzheimer's disease mice. The present data show that pharmacological antagonism of B1 receptor (R-715) but not B2 receptor (HOE-140) markedly increased nitric oxide and tumor necrosis factor alpha release from BV2 microglial cells. We also showed that intranasal treatment with R-715 but not HOE-140 of Alzheimer's mice enhanced amyloid beta burden and microglia/macrophages activation. Taken together, our data reveal a possible role for the bradykinin B1 receptor in neuroinflammation and in the control of Abeta accumulation in transgenic mice, possibly through regulation of glial cell responses.
authors.forename: Keren
authors.initials: K
authors.lastname: Asraf
authors.forename: Nofar
authors.initials: N
authors.lastname: Torika
authors.forename: Ella
authors.initials: E
authors.lastname: Roasso
authors.forename: Sigal
authors.initials: S
authors.lastname: Fleisher-Berkovich
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D065168:Bradykinin Receptor Antagonists; C120984:R 715; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C065679:icatibant; D001920:Bradykinin