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Serum deprivation and re-addition: effects on cyclooxygenase inhibitor sensitivity in cultured glia

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image of Inflammopharmacology

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 B2 (TXB2) 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 TXB2 production was considerably reduced, as was the amount of COX immunoreactivity determined by Western blotting. Basal and AA-stimulated TXB2 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 IC50 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.

Affiliations: 1: Department of Pharmacology, The School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, UK


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