Stimulation of PGE2 synthesis by mercuric chloride in rat glomeruli and glomerular cells in vitro

PGE2 production in the presence of mercuric chloride was measured by specific radioimmunoassay in isolated whole glomeruli and in cultured glomerular cells. Under basal conditions, mercuric chloride at 10 micrograms.ml-1 caused a twofold stimulation of PGE2 in isolated whole glomeruli, and at 1 to 10 micrograms.ml-1 it caused a more marked increase of PGE2 (eight times the control value) in mesangial or epithelial glomerular cells. An excess of arachidonic acid, however, blunted the stimulatory effects of mercury. Furthermore, the effect of mercuric chloride on PGE2 production was only observed with intact preparations but not with cell homogenates. Mercury inhibited cyclooxygenase activity in purified glomerular microsomes. It also inhibited phospholipase activity in purified glomerular cell membranes, whereas it stimulated phospholipase activity in intact cells. These results demonstrate that mercury modifies PGE2 synthesis via multiple mechanisms. Stimulation occurring at low doses of mercury can be attributed to the indirect activation of phospholipase. We suggest that mercuric chloride suppresses the inhibitory effect of lipomodulin on this enzyme.