High oligomycin concentrations augment 6-keto-PGF_1α production in ventricular cardiomyocytes

Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 μg/ml), either alone or combined with 2-deoxyglucose (20 mM), led to the rapid depletion of cellular ATP. Inositol (poly)phosphate production decreased, and 6-keto PGF_1α production was increased. In cells depleted of ATP, either by low oligomycin concentrations or by sodium azide, 6-keto PGF_1α was not appreciably increased. There was a 25% rise in the release of fatty acids from the sn-2 position in glycerophospholipids. We suggest that oligomycin at high concentrations causes the release of free arachidonic acid from phospholipids either by non-PIP₂-specific PLC and DG lipase or by phospholipase D, phosphatidic acid phosphatase and DG lipase. The effect is unrelated to decreased cellular ATP content.