Ethanol dependent interaction between prostaglandins and lipoxygenase products in human peripheral lymphocytes

The effect of lipoxygenase products, 12-L-HETE and 15-L-HPETE, on cyclic AMP levels in human peripheral lymphocytes was examined in the absence and in the presence of a prostaglandin of the E-type (0.6-3.0 microM) or isoprenaline (33 microM). The studies were performed either in the absence or in the presence of 6 per cent ethanol. For comparison the effect of arachidonic acid and linolenic acid were studied. In the absence of ethanol 12-L-HETE and 15-L-HPETE had no significant effect on cyclic AMP accumulation. However, in the presence of ethanol 12-L-HETE (above 1 microM) inhibited prostaglandin E1 but not isoprenaline induced cyclic AMP accumulation. 15-L-HPETE had a biphasic effect on prostaglandin E2 induced cyclic AMP accumulation. Concentrations below 1 microM stimulated, those above inhibited. Virtually complete inhibition was seen at 15 microM. The two other fatty acids inhibited both prostaglandin E2 and isoprenaline induced cyclic AMP accumulation in the presence, but not in the absence of ethanol. The results show that lipoxygense products have little or no effect on cyclic AMP accumulation in human peripheral lymphocytes unless ethanol is present. In the presence of ethanol both 12-L-HETE and 15-L-HPETE appeared to selectively affect the cyclic AMP accumulation stimulated by PGE.