title: Nitric oxide (NO) inhibits prostaglandin E2 9-ketoreductase (9-KPR) activity in human fetal membranes.
abstract: 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).
authors.affiliation: Center for Pharmacological and Botanical Studies (CEFYBO, CONICET), Laboratory of Physiopathology of Pregnancy and Labor, Paraguay 2155, C1121ABG Buenos Aires, Argentina. marifarina@yahoo.com
authors.forename: M G
authors.initials: MG
authors.lastname: Farina
authors.forename: S
authors.initials: S
authors.lastname: Billi
authors.forename: M S
authors.initials: MS
authors.lastname: Sordelli
authors.forename: M L
authors.initials: ML
authors.lastname: Ribeiro
authors.forename: G
authors.initials: G
authors.lastname: Di Girolamo
authors.forename: E
authors.initials: E
authors.lastname: Lombardi
authors.forename: A M
authors.initials: AM
authors.lastname: Franchi
mesh_terms: D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005321:Extraembryonic Membranes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C035858:prostaglandin-E2 9-reductase; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone