Modulation of prostaglandin production by nitric oxide in astroglia

Abstract

We examined the effects of exogenous nitric oxide (NO) on prostaglandin production in fetal ovine astroglia. Astroglia in secondary culture grown in 12 well plates were exposed to medium alone or medium containing 10 ng/ml interleukin 1α (IL1α), in the presence or absence of 10 and 100 μM sodium nitroprusside (SNP). Sodium nitroprusside is a NO donor. Prostaglandin F 2α (PGF 2α) levels were determined by enzyme immunoassay after 4 h of medium and/or drug application. Application of 100 μM SNP reduced basal levels of PGF 2α from 530 ± 48 pg/ml (mean ± SEM) ( n = 9) to 248 ± 60 pg/ml ( n = 8) ( P < 0.05). In IL1α treated cells, PGF 2α levels were 846 ± 109 pg/ml ( n = 9) ( P < 0.05, compared to basal levels) in the absence and 567 ± 122 pg/ml ( n = 9) in the presence of 100 μM SNP ( P < 0.05, compared to IL1α alone). We tested whether effects of exogenous NO on PGF 2α levels would be influenced by elimination of endogenously produced NO. Inhibition of NO synthase with 100 μM N G-nitro- l-arginine-methyl ester ( l-NAME) did not affect PGF 2α levels during basal conditions, or affect reductions in PGF 2α levels during application of 100 μM SNP. In addition, l-NAME application did not affect IL1α-induced increases in PGF 2α levels or reductions in PGF 2α levels with coapplication of 100 μM SNP. In contrast to the higher dose, application of 10 μM did not significantly affect PGF 2α levels. In summary, application of 100 μM SNP reduces basal production of PGF 2α and attenuates increases in PGF 2α levels with IL1α application.