Farina M G, Billi S, Sordelli M S, Ribeiro M L, Di Girolamo G, Lombardi E, Franchi A M
Center for Pharmacological and Botanical Studies (CEFYBO, CONICET), Laboratory of Physiopathology of Pregnancy and Labor, Paraguay 2155, C1121ABG Buenos Aires, Argentina.
Prostaglandins Other Lipid Mediat. 2006 May;79(3-4):260-70. doi: 10.1016/j.prostaglandins.2006.02.004. Epub 2006 Apr 17.
Nitric oxide (NO) synthesized by fetal membranes may act either directly inhibiting myometrium contractility or indirectly interacting with tocolytic agents as prostaglandins (PGs). Here we examined if NO could modulate prostaglandin E(2) 9-ketoreductase (9-KPR) activity in human fetal membranes (HFM). 9-KPR is the enzyme that converts PGE(2) into PGF(2alpha), the main PGs known to induce uterine contractility at term. Chorioamnion explants obtained from elective caesareans were incubated with aminoguanidine (AG), an iNOS inhibitor, or NOC-18, a NO donor. NOC-18 (2mM) increased PGE(2) production and diminished PGF(2alpha) synthesis in HFM. AG presented the opposite effect. When we evaluated the activity of 9-KPR by the conversion of [(3)H]-PGE(2) into [(3)H]-PGF(2alpha) and 13,14-dihidro-15-keto prostaglandin F(2alpha) (the PGF(2alpha) metabolite), we found that NOC-18 inhibited 9-KPR activity. Interestingly, AG did not elicit any effect on 9-KPR but l-NAME, a non-selective NOS inhibitor, significantly increased its activity. Our data suggests that exogenous NO inhibits 9-KPR activity in HFM, thus modulating the synthesis of important labor mediators as PGF(2alpha).
胎膜合成的一氧化氮（NO）可能直接抑制子宫肌层收缩，或间接与前列腺素（PGs）等宫缩抑制剂相互作用。在此，我们研究了NO是否能调节人胎膜（HFM）中前列腺素E2 9-酮还原酶（9-KPR）的活性。9-KPR是一种将PGE2转化为PGF2α的酶，已知PGF2α是足月时诱导子宫收缩的主要前列腺素。从选择性剖宫产获取的绒毛膜羊膜外植体与诱导型一氧化氮合酶抑制剂氨基胍（AG）或NO供体NOC-18一起孵育。NOC-18（2mM）可增加HFM中PGE2的产生，并减少PGF2α的合成。AG则呈现相反的效果。当我们通过将[³H]-PGE2转化为[³H]-PGF2α和13,14-二氢-15-酮前列腺素F2α（PGF2α代谢物）来评估9-KPR的活性时，发现NOC-18抑制了9-KPR的活性。有趣的是，AG对9-KPR没有任何影响，但非选择性一氧化氮合酶抑制剂L-NAME显著增加了其活性。我们的数据表明，外源性NO抑制HFM中9-KPR的活性，从而调节重要的分娩介质如PGF2α的合成。
