Serum deprivation and re-addition: effects on cyclooxygenase inhibitor sensitivity in cultured glia |
| |
Authors: | James Phillips Brian Pearce |
| |
Institution: | (1) Department of Pharmacology, The School of Pharmacy, 29/39 Brunswick Square, London, WC1N 1AX, UK |
| |
Abstract: | 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. |
| |
Keywords: | Cultured glia cyclooxygenases cyclooxygenase inhibitors serum deprivation serum readdition |
本文献已被 PubMed SpringerLink 等数据库收录! |
|