Isolated ductal cells of rat submandibular gland phospholipid pools were labeled with [3 H] arachidonic acid (AA). The tracer was incorporated preferentially to phosphatidylcholine (46% of the lipidic fraction). Extracellular ATP induced the release of [3 H] AA to the extracellular medium in a time-and dose-dependent manner (EC 50= 220 μ m). Among other agents tested, only 2′, 3′-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (Bz-ATP) was able to mimic the effect of ATP (EC 50= 15 μ m), without activation of phospholipase C. The purinergic antagonists oxidized ATP, suramin, and Coomassie Blue partly inhibited the response to 1 mm ATP and 100 μ m Bz-ATP; the response was also blocked by the addition of Mg 2+ or Ni 2+. Expression of P2X 7 receptor mRNA in these cells was confirmed by reverse transcription-polymerase chain reaction. In the presence of …