Inhibition of phospholipase A2 isoenzymes in human endometrium by mefenamic acid and indomethacin: modulation by calcium ions.

The inhibition of endometrial phospholipase A2 activity by the non-steroidal anti-inflammatory agents mefenamic acid and indomethacin was studied over the concentration range 1 mmol/1-0.1 mumol/l. Both phospholipase A2 type 1 (a calcium-dependent enzyme) and phospholipase A2 type 2 (a calcium-independent enzyme) were inhibited by mefenamic acid, but the magnitude of the inhibition was dependent on calcium concentration. Phospholipase A2 type 1 was inhibited 50% by 10 mumol mefenamic acid/l in the presence of 1.25-5 mmol calcium/l, but a concentration of 2.2 mmol mefenamic acid/l was required for 50% inhibition in the absence of calcium. On the other hand, phospholipase A2 type 2 was inhibited 50% by 22 mumol mefenamic acid/l in the absence of calcium and by 100 mumol mefenamic acid/l in the presence of calcium (2.5 mmol/l). Although indomethacin was a less effective inhibitor of phospholipase A2 activity, a similar relationship with calcium was demonstrated. However, indomethacin also had a stimulatory effect on phospholipase A2 type 1 activity in the absence of calcium. Our findings suggest that the two endometrial enzymes may be inhibited by different mechanisms and that the dependence of the enzyme on calcium for activation may be a contributing factor.