Document Detail

Biphasic effects of nonsteroidal anti-inflammatory drugs on prostaglandin production by cultured rat calvariae.
MedLine Citation:
PMID:  2500679     Owner:  NLM     Status:  MEDLINE    
We have studied the effects on bone of three structurally dissimilar non-steroidal anti-inflammatory drugs which inhibit prostaglandin cyclo-oxygenase activity (PGH synthase); indomethacin, flurbiprofen, and piroxicam. We used cultures of half calvaria from neonatal or fetal rats to measure effects on PGE2 production, measured by radioimmunoassay. In four day neonatal rat calvaria, indomethacin inhibited PGE2 release into the medium by 80% at 10(-8) M, while flurbiprofen and piroxicam produced similar inhibition at 10(-6) M. However, at 10(-10) M, treatment with all three compounds resulted in an increase in medium PGE2 concentration of 60 to 120%. To assess the mechanism of this effect, bones were labeled with [3H]-arachidonic acid, washed and cultured in the presence or absence of piroxicam. At 10(-6) M, piroxicam inhibited production of cyclo-oxygenase products and arachidonic acid release. However, at 10(-10) M, there was a substantial increase in labeled products, particularly PGE2, despite a further decrease in arachidonic acid release. In 21 day fetal rat cultures, flurbiprofen was found to increase PGE2 release both in control cultures and cultures which had been incubated with cortisol (10(-8) M) to reduce endogenous arachidonic acid release and supplied with exogenous arachidonic acid (10(-5) M) to provide a substrate. These results indicate that three potent inhibitors of PGH synthase can, paradoxically, increase prostaglandin production at low concentrations. The effect does not appear to be due to increased arachidonic acid release, and could be due to increased PGH synthase activity.
L G Raisz; H A Simmons; P M Fall
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Prostaglandins     Volume:  37     ISSN:  0090-6980     ISO Abbreviation:  Prostaglandins     Publication Date:  1989 May 
Date Detail:
Created Date:  1989-08-10     Completed Date:  1989-08-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0320271     Medline TA:  Prostaglandins     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  559-65     Citation Subset:  IM    
Division of Endocrinology and Metabolism, University of Connecticut Health Center, Farmington 06032.
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MeSH Terms
Animals, Newborn
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Bone and Bones / drug effects,  metabolism*
Cells, Cultured
Chromatography, High Pressure Liquid
Cyclooxygenase Inhibitors
Dinoprostone / biosynthesis*
Flurbiprofen / pharmacology
Indomethacin / pharmacology
Piroxicam / pharmacology
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase Inhibitors; 363-24-6/Dinoprostone; 36322-90-4/Piroxicam; 5104-49-4/Flurbiprofen; 53-86-1/Indomethacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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