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The cyclo-oxygenase inhibitors indomethacin and ibuprofen inhibit the insulin-induced stimulation of ribosomal RNA synthesis in L6 myoblasts.

ABSTRACT: Insulin stimulated total RNA accretion and the incorporation of [3H]uridine into RNA in L6 skeletal-muscle myoblasts. Incorporation of uridine into the rRNA was measured after either separation of 18 S and 28 S rRNA species by agarose-gel electrophoresis or separation of dissociated 40 S and 60 S ribosomal subunits on sucrose density gradients. Both methods showed a stimulation by insulin of uridine incorporation into the RNA of the two subunits. Two non-steroidal anti-inflammatory drugs, indomethacin and ibuprofen, which inhibit the metabolism of arachidonic acid by the cyclo-oxygenase pathway, inhibited the insulin-induced accretion of total cellular RNA and the incorporation of uridine into the RNA of both ribosomal subunits. The effect of insulin was observed both by using a tracer dose of [3H]uridine (5 microM) and in the presence of a high concentration (1 mM) of uridine to minimize possible changes in intracellular precursor pools. Neither insulin nor indomethacin was found to affect the incorporation of uridine into the total intracellular nucleotide pool, or the conversion of uridine into UTP. The ability of inhibitors of arachidonic acid metabolism to prevent insulin-induced increases in RNA metabolism suggests that a prostaglandin or other eicosanoid is involved in the signal mechanism whereby insulin stimulates RNA synthesis.

SUBMITTER: Palmer RM

PROVIDER: S-EPMC1133552 | biostudies-other | 1989 Nov

REPOSITORIES: biostudies-other

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Project description:BackgroundDifferences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor (coxib) are affected by drug, dose, duration, outcome definition, and patient gastrointestinal and cardiovascular risk factors. We calculated the absolute risk for each effect.MethodsWe sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal (complicated upper gastrointestinal perforations, ulcers, or bleeds, but not symptomatic or endoscopic ulcers) and serious cardiovascular outcomes (antiplatelet trial collaborators - APTC - outcome of fatal or nonfatal myocardial infarction or stroke, or vascular death).ResultsMeta-analyses and large randomised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data. In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure. Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs; serious cardiovascular events occurred at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events. In the overall comparison, for every 1000 patients treated for a year with coxib rather than NSAID, there would be eight fewer complicated upper gastrointestinal events, but one more fatal or nonfatal heart attack or stroke. Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons. For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications, and two fewer fatal or nonfatal heart attacks or strokes. For rofecoxib there would be six fewer upper gastrointestinal complications, but three more fatal or nonfatal heart attacks or strokes. For lumiracoxib there would be eight fewer upper gastrointestinal complications, but one more fatal or nonfatal heart attack or stroke.ConclusionCalculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs, serious cardiovascular events occur at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events.

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The cyclo-oxygenase inhibitors indomethacin and ibuprofen inhibit the insulin-induced stimulation of ribosomal RNA synthesis in L6 myoblasts.

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