The coumarin derivative AD6 inhibits the release of arachidonic acid by interfering with phospholipase A2 activity in human platelets stimulated with thrombin

Agents Actions. 1990 Mar;29(3-4):364-73. doi: 10.1007/BF01966469.

Abstract

AD6 is a coumarin derivative which is able to inhibit platelet aggregation and release due to various agonists as adrenaline, PAF, Ca++ ionophore and others. It has been demonstrated that this compound reduces the production of free arachidonate and diglyceride from human platelets pulse-labeled with radioactive arachidonic acid thus suggesting a possible interference with the activity of phospholipase A2 and/or phospholipase C. The present report indicates that the drug has no effect on the increase of the labeling of phosphatidic acid which takes place when platelets pulse-labeled with arachidonic acid are stimulated with thrombin. Furthermore, AD6 is not able to cause changes on the metabolism of phosphoinositides monitored using platelets pre-labeled with [3H] inositol. These observations exclude the possibility that AD6 interferes with phospholipase C activity. Experiments with platelets pulse-labeled with arachidonate suggest that AD6 inhibits phospholipase(s) A2 activity or modulate negatively one or more processes involved in its activation.

MeSH terms

  • Arachidonic Acid
  • Arachidonic Acids / blood*
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology*
  • Chromonar / analogs & derivatives
  • Chromonar / pharmacology*
  • Coumarins / pharmacology*
  • Diglycerides / blood
  • Humans
  • Inositol / blood
  • Phosphatidylcholines / blood
  • Phosphatidylinositols / blood
  • Phospholipases / antagonists & inhibitors*
  • Phospholipases A / antagonists & inhibitors*
  • Phospholipases A2
  • Phospholipids / blood*
  • Plasmalogens / blood
  • Thrombin / pharmacology*

Substances

  • Arachidonic Acids
  • Coumarins
  • Diglycerides
  • Phosphatidylcholines
  • Phosphatidylinositols
  • Phospholipids
  • Plasmalogens
  • choline plasmalogens
  • phosphatidal ethanolamines
  • Arachidonic Acid
  • Inositol
  • cloricromen
  • Phospholipases
  • Phospholipases A
  • Phospholipases A2
  • Thrombin
  • Chromonar