Serum deprivation and re-addition: effects on cyclooxygenase inhibitor sensitivity in cultured glia.
A number of drugs were assessed for their ability to inhibit stimulus-evoked prostanoid synthesis in cultured glia. These drugs included non-selective cyclooxygenase (COX) inhibitors and those considered to be selective for the inducible isoform of this enzyme (COX-2). Experiments were carried out on normal cultures and those which had been maintained in serum-free growth medium for four days then re-exposed to serum for a further seven days. All of the drugs tested elicited concentration-dependent inhibitions of arachidonic acid (AA)-stimulated thromboxane B(2) (TXB(2)) accumulation in normal cultures with the following rank order of potency: indomethacin > piroxicam > nimesulide = NS398 > ibuprofen >> aspirin > paracetamol. In cultures which had been deprived of serum for four days, basal and AA-stimulated TXB(2) production was considerably reduced, as was the amount of COX immunoreactivity determined by Western blotting. Basal and AA-stimulated TXB(2) production together with COX immunoreactivity were restored to control levels by the re-addition of serum to serum-deprived cultures for 7 days. In these cultures, the rank order of potency was: indomethacin > piroxicam >> ibuprofen > nimesulide = NS398 >> aspirin > paracetamol; however, there were marked charges in the apparent IC(50) values for particular drugs. Indomethacin, piroxicam and aspirin were very similar to control, but the potencies of ibuprofen (3-fold), NS398 (30-fold) and nimesulide (40-fold) were found to be decreased when compared to control. Paracetamol, on the other hand, was found to be almost 3-fold more potent under these conditions. Glia appear to express a COX with a novel sensitivity to particular inhibitors following serum deprivation and re-addition.
Phillips
James
J
Department of Pharmacology, The School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, UK.
Pearce
Brian
B
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D044967:Serum / Q000502:physiology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D016895:Culture Media, Serum-Free; D052246:Cyclooxygenase 2 Inhibitors; D016718:Arachidonic Acid; D013929:Thromboxane B2