Decrease of cellular ATP by dihexanoylglycerol may limit responses to protein kinase C activation

1,2-sn-Dihexanoylglycerol (HHG) reduced the ATP content of HL-60 cells. This concentration-related (10-100 microM) effect reached a maximum of over 90%, was enantiomerically specific and not accompanied by release of lactate dehydrogenase. Oleoylacetylglycerols (3-100 microM) had no effect on ATP levels while phorbol dibutyrate (PDBu, 0.01-1 microM) decreased ATP content of HL-60 cells by up to 40%. Responses stimulated by HHG became limited as the concentration was increased above 10 microM, this being manifest as either a low maximum response compared to PDBu (superoxide release) or a bell-shaped concentration-effect curve (degranulation). HHG (30-100 microM) inhibited PDBu-stimulated superoxide release, this inhibition being enantiomerically specific. It is probable that the effect of HHG on ATP content impairs cellular responses mediated through protein kinase C activation.