Phillips, James Benjamin;
(2000)
Cyclooxygenase activity and expression in glial cells.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
In this study, a panel of inhibitors with a range of selectivities for the two cyclooxygenase isoforms (COX-1 and -2) was used to probe the contribution of each to the synthesis of thromboxane B2 (TXB2) in cultured glia after stimulation with A23187 or arachidonic acid. Mixed glial cell cultures (~95% astrocytes, 5% microglia) were prepared from the cortices of newborn rat pups and maintained in vitro for 14 days. Controversy exists as to the contribution of astrocytes and microglia to the prostanoid synthetic capacity of mixed glial cell cultures. In order to investigate this, derivative cultures were made which were enriched in either astrocytes or microglia. Both astrocytes and microglia were found to express COX protein, and TXB2 production was inhibited in each by inhibitors preferential for the different COX isoforms suggesting that both COX-1 and COX-2 contributed to TXB2 synthesis in both cell types. Removal of serum from the culture medium for 4 days caused a decrease in the level of basal and stimulated TXB2 synthesis, with a concomitant decrease in the presence of COX protein. There was also a decrease in potency of COX-2 selective inhibitors suggesting that the removal of serum caused a down-regulation of COX-2 expression. COX protein expression and TXB2 synthesis were restored to control levels 7 days after serum re-addition, but the inhibitor profile subsequently obtained showed a pattern which differed considerably from either control or serum-deprived cells. Of particular note was an increase in the potency of paracetamol after serum re-addition. The effect of nitric oxide (NO) donors on COX activity in mixed glial cells under normal culture conditions was also investigated. Although inhibition of endogenous NO production was without effect, NO donors reduced stimulus-induced TXB2 release. This was found to be independent of the COX isoform present in the cells and was additive with that evoked by COX inhibitors.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Cyclooxygenase activity and expression in glial cells |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Biological sciences; Glial cells |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10102560 |
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