Nitric oxide inhibits prostanoid synthesis in the rat oviduct.
We have studied the effect of nitric oxide (NO) on the production of arachidonic acid ([14C]-AA) metabolites in the rat oviduct. The basal synthesis of eicosanoids was measured by the conversion of ([14C]-AA) to the different radiolabeled products of cyclooxygenase (COX). The oviducts incubated for 1 h with the labeled substrate of COX were able to convert 3.3 +/- 0.3% of ([14C]-AA) to 6-ceto-PGF1alpha, 10.7 +/- 1.0% to PGF2alpha, 13.5 +/- 1.2% to PGE2 and 6.3 +/- 0.5% to TXB2. The tissues were incubated with different doses of two NO donors: SIN-1 and Spermine NONOate. The results indicated that SIN-1 produces a significant decrease (50%; P < 0.05) in all prostanoids evaluated in a dose-response fashion. The inhibitory effect was completely reversed by addition of 20 microg/ml of hemoglobin (Hb), a NO scavenger. The addition of Spermine NONOate to the incubation medium diminished significantly (65%) the synthesis of COX metabolites suggesting that NO acts by inhibiting COX activity in the rat oviduct. However, NOS inhibitors, N(G)-L-arginine-methyl-ester (L-NAME) nd N(G)-L-monomethyl-arginine (L-NMMA) had no effect on basal production of the prostanoids. These results indicate that in the rat oviduct the synthesis of COX metabolites is negatively regulated by nitric oxide.
Perez Martinez
S
S
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Cientificas y Técnicas, Buenos Aires, Argentina.
Farina
M
M
Ogando
D
D
Ribeiro
M L
ML
Gimeno
M
M
Franchi
A M
AM
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D005187:Fallopian Tubes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009589:Nitrogen Oxides; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology
D002250:Carbon Radioisotopes; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D011453:Prostaglandins; C091861:spermine nitric oxide complex; D016718:Arachidonic Acid; D013096:Spermine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases