Regulation of arachidonic acid metabolism by phenylarsine oxide

Abstract

Preincubation of rat liver cells (the C-9 cell line) for 25 min with phenylarsine oxide at levels ranging from 0.06 to 0.6 μM amplifies prostaglandin I 2 production when subsequently stimulated by platelet activating factor, lysine vasopressin, bradykinin, thapsigargin, and the Ca 2+ ionophore, A-23187, but not that stimulated by exogenous arachidonic acid. The amplification is decreased after preincubation for 25 min with 1.8 μM phenylarsine oxide. Preincubation of mouse lymphoma cells (the WEHI-3 cell line) with phenylarsine oxide at levels ranging from 0.06 to 1.8 μM for 60 min does not affect prostaglandin E 2 levels but inhibits leukotriene B 4 and C 4 production stimulated by the Ca 2+-ionophore, A-23187. Amplification of prostaglandin production by phenylarsine oxide is reversed 100 times more effectively by 2,3-dimercaptopropanol than by 2-mercaptoethanol. Deesterification of lipids appears to be regulated positively in rat liver cells and leukotriene production negatively in mouse lymphoma cells by phosphorylation of tyrosine.