Arachidonic acid metabolism and casein secretion in lactating rabbit mammary epithelial cells : Effects of inhibitors of prostaglandins and leukotrienes synthesis

Abstract

The metabolism of arachidonic acid (AA) in fragments of lactating rabbit mammary glands in vitro was studied by considering the distribution of 13-{ 14C}AA in the cells, and the effects of inhibitors of cyclooxygenase and lipoxygenase pathway on the basal and prolactin (PRL)-stimulated casein secretion. 13-{ 14C}AA was incorporated in all classes of lipids and PRL increased transiently the percentage of free fatty acid after 1 and 5 min. Ten μM ETYA (5,8,11,14-Eicosatetraynoic acid), a tetrayne analogue of AA inhibited prostaglandins F 2α (PGF 2α) production but not leukotrienes B 4 and C 4 (LTB 4 and LTC 4) production and increased basal casein secretion. 10 −4 M DCHA (Docosahexaenoic acid) a competitive inhibitor of prostaglandin-synthetase inhibited PGF 2α production but did not affect basal nor PRL-stimulated casein secretion. Fourteen μM indomethacin inhibited PFF 2α and LTC 4 production and PRL-stimulated casein secretion. Ten μM NGDA (nordihydroguaiaretic acid) an inhibitor of lipoxygenase pathway, inhibited LTB 4 and LTC 4 production, increased basal level of casein secretion and inhibited PRL-stimulated casein secretion. Hundred μM caffeic acid, an inhibitor of glutathion-S-transferase (GST), a class of enzymes implied in the transformation of LTA 4 into LTC 4, had the same effect that NDGA on basal and PRL-stimulated casein secretion. These findings show that inhibitors of AA metabolites alter casein secretion.