Effect of exogenous phospholipase A2 and triacylglycerol lipase on the synthesis and release of monoenoic and bisenoic prostaglandins from isolated rat uterus

The possible existence of a selective and independent mechanism subserving the formation of prostaglandin E₁ (PGE₁) and of prostaglandin E₂ (PGE₂) has been reported in previous studies from our group. In the present experiments we have demonstrated that neutral lipid lipases play an important role yielding dihomo-gamma-linolenic acid for the formation of PGE₁. Indeed, exogenous triglyceride lipase added to the incubation bathing solution at a concentration of 150 U/ml increased several fold the production of PGE₁ by isolated uterine strips obtained from spayed rats. Nevertheless the presence of the enzyme did not modify significantly the synthesis and release of bisenoic PGs (PGE₂ and PGF_2α). When triarachidonin was added, as an artificial substrate into the incubating medium in order to detect the presence of endogenous triacylglycerol lipase, we observed a significant increment in the generation of PGE₂ (p < 0.005) and of PGF_2α (p < 0.001) without evident changes in the basal release of PGE₁. On the other hand, the addition of phospholipase A₂ (PLA₂) at 0.2 U/ml, increased significantly the production of PGE₂ (p < 0.001) but failed to alter the concentration of PGE₁ in the incubating solution. Surprisingly, PLA₂ did not enhance the synthesis of PGF_2α in the present experiments, a situation for which we do not have a clear explanation. Exogenous bradykinin (10⁻⁶ M), a well known stimulant of PLA₂ activity in several tissues, also increased significantly (p < 0.001) the production of PGE₂ without altering that of PGE₁. Results presented herein provide strong support to the notion that different enzyme mechanisms and different lipid stores are linked to the formation of PGE₁ and PGE₂ in isolated rat uteri.