Effects of inhibitors of arachidonic acid turnover on the production of prostaglandins by the guinea-pig uterus

The supply of free arachidonic acid from phospholipids is generally regarded as the rate-limiting step for prostaglandin (PG) synthesis by tissues. Two enzymes involved in arachidonic acid uptake into, and release from, phospholipids are acyl-CoA:lysophospholipid acyltransferase (ACLAT) and phospholipase A(2) (PLA(2)), respectively. PGF(2 alpha) produced by the endometrium induces luteolysis in several species including guinea-pigs. Thimerosal, an inhibitor of ACLAT, and aristolochic acid, an inhibitor of PLA(2), both reduced, in a concentration-dependent manner, the output of PGF(2 alpha) from guinea-pig endometrium cultured for 24 h on days 7 and 15 of the oestrous cycle. This study showed that the continual production of PGF(2 alpha) by guinea-pig endometrium is not only dependent upon the activity of PLA, for releasing free arachidonic acid for PGF(2 alpha) synthesis, but also on the incorporation of arachidonic acid into the phospholipid pool by the activity of ACLAT. The inhibitory effects of thimerosal and aristolochic acid on the outputs of PGE(2) and 6-keto-PGF(1 alpha) were less marked, particularly on day 7 when the low output of PGE(2) was unaffected and the output of 6-keto-PGF(1 alpha) was increased at the lower concentrations of thimerosal. This finding indicates that there are different pools of arachidonic acid bound as phospholipid for the syntheses of PGF(2 alpha) and 6-keto-PGF(1 alpha) by guinea-pig endometrium.