A novel enhancing effect of platelet activating factor (PAF) on glucose oxidation in uteri from pregnant rats. Participation of prostaglandins and leukotrienes

Abstract

The effects of platelet activating factor (PAF) on glucose oxidation in uterine strips isolated from rats in the 4 th and 5 th day of pregnancy, were explored. PAF, at a concentration of 10 −10 and 10 −8 M, augmented significantly the generation of 14CO 2 from labelled glucose in uteri from pregnant rats in the 4 th day of pregnancy. When the tissue was obtained from 5 days pregnant rats, the addition of PAF at 10 −8 increased significantly more than PAF at 10 −10 M the metabolism of glucose. On the other hand, PAF at 10 −8 M failed to alter the uterine basal production of 14CO 2 from labelled glucose in animals at estrus. BN52021, a specific PAF antagonist employed at 10 −5 M, blocked completely the action of PAF in the pregnant rat uterus. PGE 1, PGE 2 and PGF 2α enhanced significantly the formation of 14CO 2 from labelled glucose in uteri from 5 days pregnant rats. Indomethacin, a well known inhibitor of prostaglandin synthesis, did not alter the basal glucose metabolism in uteri from 5 days pregnant rats, but antagonized completely the stimulating action of PAF on 14CO 2 production from labelled glucose an effect that was partially reverted by the addition of PGE 1, PGE 2 or PGF 2α (10 −7 M). Furthermore, nordihydroguaiaretic acid (NDHGA), a specific inhibitor of 5-lipoxygenase at 10 −5 M, as well as FPL-55712, an antagonist of leukotrienes (LTs), at the same concentration, blocked the action of PAF on the metabolism of glucose. The action of NDHGA was partially counteracted by the addition of LTC 4 at 10 −7 M. Considering all these results, we suggest that PAF stimulates indirectly glucose metabolism via the “de novo” synthesis of PGs anb LTs, probably by the activation of phospholipase A 2 (PLA 2). As far as we know the present report represent the first description of a stimulating action of PAF on glucose metabolism in pregnant rat uteri.