title: The coumarin derivative AD6 inhibits the release of arachidonic acid by interfering with phospholipase A2 activity in human platelets stimulated with thrombin.
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.
authors.affiliation: Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Porcellati
authors.forename: V
authors.initials: V
authors.lastname: Costantini
authors.forename: M
authors.initials: M
authors.lastname: Prosdocimi
authors.forename: M
authors.initials: M
authors.lastname: Stasi
authors.forename: R
authors.initials: R
authors.lastname: Pistolesi
authors.forename: G G
authors.initials: GG
authors.lastname: Nenci
authors.forename: G
authors.initials: G
authors.lastname: Goracci
mesh_terms: D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002866:Chromonar / Q000031:analogs & derivatives / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004075:Diglycerides / Q000097:blood; D006801:Humans; D007294:Inositol / Q000097:blood; D010713:Phosphatidylcholines / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010743:Phospholipids / Q000097:blood*; D010955:Plasmalogens / Q000097:blood; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D001095:Arachidonic Acids; D003374:Coumarins; D004075:Diglycerides; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010743:Phospholipids; D010955:Plasmalogens; C032459:choline plasmalogens; C020791:phosphatidal ethanolamines; D016718:Arachidonic Acid; D007294:Inositol; C025945:cloricromen; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin; D002866:Chromonar