Bradykinin increases resensitization of purinergic receptor signaling in glioma cells

BACKGROUND: Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells. Bradykinin is also an important paracrine mediator which is highly expressed in brain tumors and may correlate with their pathological grade. Interaction between bradykinin and purinergic signaling may therefore be involved in the regulation of glial tumor cells. RESULTS: We examined the effect of bradykinin on glial purinergic signaling in an immortalized glioma cell line. Confocal calcium imaging revealed that ATP evokes an increase in [Ca(2+)](i )in the U87 human astrocytoma cell line. This response was reduced with repetitive application of ATP, likely due to receptor desensitization. However exposure to bradykinin increased the Ca(2+ )response to a second application of ATP, consistent with increased resensitization. The bradykinin effect on resensitization was similar in the absence of extracellular Ca(2+ )or in the presence of the PKC activator PMA, but was inhibited by the protein phosphatase inhibitor okadaic acid and the PI3K inhibitor LY294002. CONCLUSIONS: Modulation of protein phosphatases and the PI3K pathway may represent a mechanism by which bradykinin potentiates purinergic signaling in glial cells.