Journal
MOLECULAR PHARMACOLOGY
Volume 69, Issue 6, Pages 1975-1983Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/mol.105.020164
Keywords
-
Categories
Ask authors/readers for more resources
In the brain, arachidonic acid ( AA) plays a critical role in the modulation of a broad spectrum of biological responses, including those underlying neuroinflammation. By using microfluorometry, we investigated the action of extracellular AA in the modulation of the purinoceptor P2X7-mediated elevation of [Ca2+](i) in cultured neocortical type-1 astrocytes and P2X7-, P2X2-transfected human embryonic kidney (HEK) 293 cells. We report that in cultured astrocytes, AA-induced [Ca2+](i) elevation is coupled to depletion of intracellular Ca2+ stores and to a sustained noncapacitative Ca2+ entry. AA also induced a robust potentiation of the astrocytic P2X7-mediated [Ca2(+)](i) rise evoked by the selective agonist 3'-O-(4-benzoyl)benzoyl-ATP ( BzATP). Pharmacological studies demonstrate that the selective P2X7 antagonists oxidized ATP and Brilliant Blue G abrogated the AA-mediated potentiation of BzATP-evoked [Ca2+](i) elevation. Fluorescent dye uptake experiments showed that the AA-induced increase in [Ca2+](i) was not due to a switch of the P2X7 receptor from channel to the pore mode of gating. The synergistic effect of AA and BzATP was also observed in HEK293 cells stably expressing rat and human P2X7 but not in rat P2X2. Control HEK293 cells responded to AA exposure only with a transient [Ca2+](i) elevation, whereas in those expressing the P2X7 receptor, AA elicited a potentiation of the BzATP-induced [Ca2+](i) rise. Together, these findings indicate that AA mediates a complex regulation of [Ca2+](i) dynamics also through P2X7- mediated Ca2+ entry, suggesting that variations in AA production may be relevant to the control of both the temporal and spatial kinetics of [Ca2+](i) signaling in astroglial cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available