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  • Title: Bradykinin stimulates glutamate uptake via both B1R and B2R activation in a human retinal pigment epithelial cells.
    Author: Lim SK, Park MJ, Jung HK, Park AY, Kim DI, Kim JC, Bae CS, Kim KY, Yoon KC, Han HJ, Park SH.
    Journal: Life Sci; 2008 Dec 05; 83(23-24):761-70. PubMed ID: 18948121.
    Abstract:
    AIMS: We were to examine the effect of bradykinin (BK) in the regulation of glutamate transporter and its related signaling molecules in a human retinal pigment epithelial (ARPE) cells, which are important cells to support retina. MAIN METHODS: d-[2,3-(3)H]-aspartate uptake, western immunoblotting, reverse transcription polymerase chain reaction, [(3)H]-arachidonic acid release, and siRNA transfection techniques were used. KEY FINDINGS: BK stimulated glutamate uptake as well as the mRNA expression of excitatory amino acid transporter 4 (EAAT4) and excitatory amino acid carrier 1 (EAAC1), which was blocked by treatment with bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R) siRNA, suggesting the role of B1R and B2R in this process. The BK-induced stimulation of glutamate uptake was also blocked by [des-Arg(10)]-HOE 140, a B1R antagonist, and HOE 140, a B2R antagonist, as well as by the tyrosine kinase inhibitors genistein and herbimycin A. In addition, the BK-induced stimulation of glutamate uptake was blocked by treatment with the phospholipase A(2) inhibitors mepacrine and AACOCF(3), the cyclooxygenase (COX) inhibitor indomethacin, and the COX-2 inhibitor Dup 697. Furthermore, the BK-induced increase in COX-2 expression was blocked by the PI-3 kinase inhibitors wortmannin and LY294002, Akt inhibitor, and the protein kinase C (PKC) inhibitors staurosporine and bisindolylmaleimide I, suggesting the role of PI-3 kinase and PKC in this process. BK stimulated Akt activation and the translocation of PKC activation via the activation of B1R and B2R. SIGNIFICANCE: BK stimulates glutamate uptake through a PKC-Akt-COX-2 signaling cascade in ARPE cells.
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