Nitric oxide inhibits prostanoid synthesis in the rat oviduct

We have studied the effect of nitric oxide (NO) on the production of arachi donic acid ([C-14]-AA) metabolites in the rat oviduct. The basal synthesis of eicosanoids was measured by the conversion of ([C-14]-AA) to the differe nt radiolabeled products of cyclooxygenase (COX). The oviducts incubated fo r 1h with the labeled substrate of COX were able to convert 3.3 +/- 0.3 % o f ([C-14]-AA) to 6-ceto-PGF(1 alpha), 10.7 +/- 1.0% to PGF(2 alpha), 13.5 /- 1.2% to PGE(2) and 6.3 +/- 0.5 % to TXB2. The tissues were incubated wit h 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 al l prostanoids evaluated in a dose-response fashion. The inhibitory effect w as completely reversed by addition of 20 mu g/ml of hemoglobin (Hb), a NO s cavenger. The addition of Spermine NONOate to the incubation medium diminis hed significantly (65%) the synthesis of COX metabolites suggesting that NO acts by inhibiting COX activity in the rat oviduct. However, NOS inhibitor s, N-G-L-arginine-methyl-ester (L-NAME) nd N-G-L-monomethyl-arginine (L-NMM A) had no effect on basal production of the prostanoids. These results indi cate that in the rat oviduct the synthesis of COX metabolites is negatively regulated by nitric oxide. (C) 2000 Harcourt Published Ltd.