ATP-evoked arachidonic acid mobilization in astrocytes is via a P2Y-purinergic receptor.
To reveal more of the mechanism whereby ATP induces arachidonic acid (AA) mobilization in astrocytes, primary cell cultures prelabeled with [3H]AA were exposed to ATP and various analogs. Release of 3H was dose and time dependent and was inhibited by blocking ATP binding. The potencies of a range of ATP analogs in mobilizing AA were consistent with that predicted for the involvement of a P2Y-purinergic receptor. Mobilization of AA was not due to non-specific cell permeabilization, as assessed by leakage of cytoplasmic lactate dehydrogenase. AA mobilization by ATP was reduced when mobilization of intracellular calcium was inhibited and in the absence of extracellular calcium. Thapsigargin, which induces release of intracellular calcium, evoked mobilization of AA and thromboxane formation, findings similar to the effects of ATP. These results suggest that ATP stimulates AA mobilization via a P2Y-purinergic receptor and that, although extracellular calcium is involved, mobilization of intracellular calcium activates phospholipase A2.
Bruner
G
G
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City.
Murphy
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D010743:Phospholipids / Q000378:metabolism; D011983:Receptors, Purinergic / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013931:Thromboxanes / Q000378:metabolism; D013997:Time Factors
D001095:Arachidonic Acids; D010743:Phospholipids; D011983:Receptors, Purinergic; D013729:Terpenes; D013931:Thromboxanes; D016718:Arachidonic Acid; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002118:Calcium