Abstract
Human platelets incubated with thrombin and indomethacin (50 microgram/ml) exhibit an accumulation of diglyceride larger and more persistent than that observed for platelets incubated with thrombin alone. The accumulation appears to be due to the impaired metabolism of diglyceride by diglyceride lipase. In preparations of broken platelets, indomethacin leads to inhibition of diglyceride lipase. A similar inhibition can be achieved by the addition of soybean lipoxidase, and both inhibitions can be counteracted by reduced glutathione. Further, hydroperoxyeicosatetraenoic acid (100 microM) markedly depresses diglyceride lipase activity, whereas neither the hydroxy derivative nor eicosatetraenoic acid displays a comparable effect. Indomethacin at concentrations comparable to those impairing diglyceride lipase does not inhibit diglyceride kinase. This report constitutes the first evidence for the functioning of diglyceride lipase in normal stimulated platelets, and points to a possible role for fatty acid hydroperoxides in governing the activity of this enzyme.
Highlights
Human platelets incubated with thrombin and indomethacin (60 pg/ml) exhibit an accumulation of diglyceride larger and more persistent than that observed for platelets incubated with thrombin alone
In preparations of broken platelets, indomethacin leads to inhibition of diglyceride lipase
As previously reported (l), platelets exposed to tbrombin showed a transient accumulation of diglyceride, quantitated either with respect to mass or to radiolabeling with [3Hs]arachidonic acid
Summary
Human platelets incubated with thrombin and indomethacin (60 pg/ml) exhibit an accumulation of diglyceride larger and more persistent than that observed for platelets incubated with thrombin alone. Bell et al [6] recently reported the presence in human platelets of a diglyceride-specific lipase which could provide an alternative pathway for the metabolism of diglyceride. The significance of this pathway as a potential means of providing arachidonic acid for utilization by platelet cyclooxygenase was noted by these investigators, a role for the enzyme was not documented for whole cells. Indomethacin inhibits diglyceride lipase in broken platelet preparations, while having no apparent effect on diglyceride kinase activity. It is possible to counteract partially such inhibition in broken platelets by the addition of reduced glutathione, and to mimic the inhibition using either soybean lipoxidase or 15-hydroperoxyeicosatetraenoic acid
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