Abstract
BackgroundPurinergic 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.ResultsWe 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 [Ca2+]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 Ca2+ response to a second application of ATP, consistent with increased resensitization. The bradykinin effect on resensitization was similar in the absence of extracellular Ca2+ or in the presence of the PKC activator PMA, but was inhibited by the protein phosphatase inhibitor okadaic acid and the PI3K inhibitor LY294002.ConclusionsModulation of protein phosphatases and the PI3K pathway may represent a mechanism by which bradykinin potentiates purinergic signaling in glial cells.
Highlights
Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells
adenosine 5’ triphosphate (ATP) is a key messenger for the intercellular communication of calcium waves, in which increases in [intracellular calcium concentration (Ca2+]i) propagate from cell to cell across multiple cells [3,4,5]
Glial cells respond to ATP through P2 purinergic receptors that belong to two families: P2Y G protein
Summary
Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells. Glial cell calcium waves have been characterized extensively in vitro in a variety of different tissue preparations, and more recently in vivo in rodent cortex and retina [6,7,8,9,10]. They are thought to play physiological roles in the modulation of neuronal activity and vascular function, in addition to contributing to pathological processes such as cortical spreading depression and seizures [11,12]. Purinergic signaling is believed to play an important role in the development and proliferation of glial cells under both physiological and pathological conditions, including those associated with glial tumors [13,14,15].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
