Steroid hormones inhibit induction of spontaneous nitric oxide production in cultured hepatocytes without changes in arginase activity or urea production.
The spontaneous formation of nitrites was examined in the medium of cultured rat hepatocytes and taken as a measure of nitric oxide generation. The rate of nitrite formation increased after 8-12 hr in culture which was blocked by the addition of dexamethasone, actinomycin D, or cycloheximide. Various glucocorticoids, mineralocorticoids, and sex steroids also inhibited nitrite formation by varying degrees, without affecting arginase activity or urea production. The inhibition of nitric oxide formation appears, therefore, not to be due to changes in the availability of arginine. The results suggest that nitric-oxide synthase is induced in hepatocytes in culture and show that anti-inflammatory glucocorticoids are not the only steroids that inhibit nitric oxide formation.
Pittner
R A
RA
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spitzer
J A
JA
D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008901:Mineralocorticoids / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D013256:Steroids / Q000494:pharmacology*; D014508:Urea / Q000378:metabolism*; D019323:omega-N-Methylarginine
D005938:Glucocorticoids; D006728:Hormones; D008901:Mineralocorticoids; D013256:Steroids; D003609:Dactinomycin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D014508:Urea; D001120:Arginine; D003513:Cycloheximide; D001119:Arginase