Influence of interleukin-1 α and COX-2 over the metabolism of arachidonic acid and glucose in isolated uterus of restricted diet rats

Abstract

Isolated uteri from rats fed with a normal diet convert [ 14C]arachidonate into eicosanoids: PGE 2, PGF 2 α , TXB 2 and 6-keto-F 1 α . Restricted diet (50% of the normal diet, during 25 days) diminishes the levels of PGE 2, PGF 2 α and TXB 2. The addition of Interleukin-1 α to the Krebs–Ringer bicarbonate medium increases sharply the production of eicosanoids. Inhibitors of nitric oxide synthase, Nω-nitro- l-arginine methyl ester or aminoguanidine, do not prevent eicosanoids increase. Conversely, NS-398 (a selective inhibitor of COX-2) blocks the increase of eicosanoids while PGE 2 blocks eicosanoids production mediated by IL-1 α. Other experiments with uteri of underfed rats confirm that interleukin-1 α produces an increase in the glucose metabolism. The addition of Nω-nitro- l-arginine methyl ester, aminoguadinine or NS-398 blocked such stimulation. It is concluded that Interleukin-1 α produces an increase of glucose metabolism in uteri isolated from underfed rats by two different mechanisms, both involving COX-2: (1) nitric oxide independent and (2) nitric oxide dependent.