MODULATION OF PROSTAGLANDIN PRODUCTION BY NITRIC-OXIDE IN ASTROGLIA

We examined the effects of exogenous nitric oxide (NO) on prostaglandi n production in fetal ovine astroglia. Astroglia in secondary culture grown in 12 well plates were exposed to medium alone or medium contain ing 10 ng/ml interleukin 1 alpha(IL1 alpha), in the presence or absenc e of 10 and 100 mu M sodium nitroprusside (SNP). Sodium nitroprusside is a NO donor. Prostaglandin F-2 alpha (PGF(2 alpha)) levels were dete rmined by enzyme immunoassay after 4 h of medium and/or drug applicati on. Application of 100 mu M SNP reduced basal levels of PGF(2 alpha) f rom 530 +/- 48 pg/ml (mean +/- SEM) (n = 9) to 248 + 60 pg/ml (n = 8) (P < 0.05). In IL1 alpha treated cells, PGF,, 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 mu M SNP (P < 0.05, c ompared to IL1 alpha alone). We tested whether effects of exogenous NO on PGF(2 alpha) levels would be influenced by elimination of endogeno usly produced NO. Inhibition of NO synthase with 100 mu M N-G-nitro-L- arginine-methyl ester (L-NAME) did not affect PGF(2 alpha) levels duri ng basal conditions, or affect reductions in PGF(2 alpha) levels durin g application of 100 mu M SNP. In addition, L-NAME application did not affect IL1 alpha-induced increases in PGF(2 alpha) levels or reductio ns in PGF(2 alpha) levels with coapplication of 100 mu M SNP. In contr ast to the higher dose, application of 10 mu M did not significantly a ffect PGF(2 alpha) levels. In summary, application of 10 mu M SNP redu ces basal production of PGF(2 alpha) and attenuates increases in PGF(2 alpha) levels with IL1 alpha application.