Relative activities of rat and dog platelet phospholipase A2 and diglyceride lipase. Selective inhibition of diglyceride lipase by RHC 80267.

RHC 80267, 1,6-di(O-(carbamoyl)cyclohexanone oxime)hexane, is a potent and selective inhibitor (I5o = 4 CM) of canine platelet diglyceride lipase. This agent had no effect on rat platelet phospholipase C at 300 p~ and only slight activity at 100 BM (15% inhibition) against rat platelet phospholipase Az. In the course of studying the effect of this agent on diglyceride lipase, it was found that this enzyme could easily be obtained from dog platelets but was much more difficult to detect in the enzyme-rich supernatants obtained from rat platelets. RHC 80267 inhibited the diglyceride lipases obtained from the platelets of both species. Detectable phospholipase Az activity was not found in the enzyme extracts prepared from dog platelets whether assayed at pH 9.0 with 5 mM CaClz or at pH 7.0 with 0.1 H ~ M CaClZ. Phospholipase AZ activity was easily detected in both soluble and particulate fractions prepared from rat platelets. An activity was detected at pH 7.0 with 0.1 mM CaClz in the rat platelet extracts, which may be due to phospholipase AI. Such activity was not found in the dog platelet extracts. Phospholipase C activity was easily detectable in the extracts of platelets from both species. We postulate that the observed differences in enzyme distribution suggest that future studies will reveal differences in the metabolism of phospholipids in the platelets of these two species. The diglyceride lipase inhibitor RHC 80267 may be useful in future studies of lipid and phospholipid metabolism in platelets and other cell types.