AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonyl-meth oxy coumarin) inhibits the release of arachidonic acid in human platelets stimulated by thrombin.

The coumarin derivative AD6 is known to inhibit platelet aggregation and release and it possesses vasodilatory properties on coronary arteries of laboratory animals. Furthermore, the inhibition of the production of TxB2 from endogenous substrates after stimulation of human platelets with collagen has been demonstrated. The present report demonstrates that AD6 inhibits the production of labeled arachidonic acid and diglycerides from phospholipids of platelets stimulated with thrombin. This effect is dose-dependent and is already evident at a concentration of the drug (25 microM) which is unable to prevent the aggregation. Apparently, AD6 inhibits the release of arachidonic acid from phosphatidylinositol and choline phosphoglycerides which are the main sources of the substrate for the synthesis of prostaglandins and thromboxanes.

Cholinephosphotransferase activity in human platelets.

Disrupted human platelets possess a cholinephosphotransferase activity (EC 2.7.8.2) whose properties have been studied in this work. The labeling of choline glycerophospholipid (CGP) from radioactive cytidine-5'-diphosphate choline (CDP-choline) in vitro shows a maximum at pH 8.0 (using Hepes [4-(2-hydroxyethyl)-piperazine-1-ethane-2-sulfonic acid] as a buffer) and is stimulated by Mn2+, Mg2+ and diacylglycerol. The enzymic activity is inhibited by Ca2+. The dependence of human platelet cholinephosphotransferase upon CDP-choline concentration does not follow the Michaelis-Menten equation. CMP strongly inhibits the reaction. The functional implications of this newly discovered platelet activity are briefly considered.