HIGH OLIGOMYCIN CONCENTRATIONS AUGMENT 6-KETO-PGF(1-ALPHA) PRODUCTIONIN VENTRICULAR CARDIOMYOCYTES

Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 mug/ml), either alone or combined with 2-deoxyglu cose (20 mM), led to the rapid depletion of cellular ATP. Inositol (po ly)phosphate production decreased, and 6-keto PGF1alpha production was increased. In cells depleted of ATP, either by low oligomycin concent rations or by sodium azide, 6-keto PGF1alpha was not appreciably incre ased. 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 phosph olipids either by non-PIP2-specific PLC and DG lipase or by phospholip ase D, phosphatidic acid phosphatase and DG lipase. The effect is unre lated to decreased cellular ATP content.