| Abstrakt: |
To investigate the role of glutathione (GSH) on prostaglandin (PG) synthesis, isolated rabbit spleens were perfused with Tyrode's solution with or without the addition of diethyl maleate (DEM) in concentrations up to 1 mM. In the absence of DEM, PG synthesis was stimulated by the Ca ionophore A23187 (20 nmole) or arachidonate (0.4 μmole). Prostaglandin (PG) E was a major product, accounting for 60-70% of the total cyclooxygenase products. Small amounts of PGFα, 6-keto-PGFα, PGD and thromboxane (Tx) B were also produced. When DEM was added to the perfusion medium, GSH content decreased dose-dependently with increasing DEM concentration. Lactate dehydrogenase activity was not detected in the venous effluent, indicating that DEM depleted intrasplenic GSH without causing any lysis of cellular membranes. A23187-induced production of PGs and of Tx was decreased with increasing concentrations of DEM up to 0.5 mM, whereas at 1.0 mM DEM, these products showed a tendency to increase as compared with levels at 0.5 mM DEM. However, this increase was only significant for TxB, which returned to levels obtained in the absence of DEM. DEM 1 mM did not cause cell lysis, but it appears to perturb the cell membrane to a degree similar to that which occurs with stimulation of phospholipase A. The small but significant increase of TxB with 1.0 mM DEM could be a result of decreased PGE isomerase activity. Perfusion with arachidonate gave virtually identical results: 1.0 mM DEM attenuated the production of all prostanoids except for TxB as compared with untreated controls. These results suggest that GSH contributes to the regulation and/or maintenance of PGs synthesis. [ABSTRACT FROM AUTHOR] |
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