The effect of MS on endothelial cell prostaglandin (PG) production and cyclooxygenase (COX) mRNA expression was examined in cultured brain endothelial cells from newborn pig cerebral microvessels; grown to confluence and treated with MS (100 ng/ml media) or naloxone (100 ng/ml media). The control cells were treated with an equivalent volume of saline. The cells were exposed to drug or saline for 0 to 96 hours. At the end of each experimental time (n=6 flasks), media was analyzed for PG levels by enzyme immunoassay. The cells were examined for COX-1 and COX-2 mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). MS exposure resulted in significant elevations in vasodilator PG levels (table).

Table 1 No caption available.
Full size table

MS had no effect on PGF2α or thromboxane B2. No differences in PG levels were detected between naloxone-treated and control groups. In the morphine-treated cells, COX-1 mRNA was significantly more expressed at 24 hr (40%, p<0.05) to 96 hr (59%,p<0.05). However, COX-2 expression was significantly lower at 24 hr (68%, p<0.05), 48 hr (52%, p<0.05), and 96 hr(39%, p<0.05) compared to the control group. We conclude that MS increases vasodilator prostaglandins in brain endothelial cells. The vasodilator responses to MS may be mediated in part through this mechanism.

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