Evidence that cytosolic phospholipase A2 is down-regulated by protein kinase C in intact human platelets stimulated with fluoroaluminate.
We reported that protein kinase C (PKC) inhibitors increase the release of arachidonic acid induced by fluoroaluminate (AlF4-), an unspecific G-protein activator, in intact human platelets. Now we demonstrate that this effect is independent of the extracellular Ca2+ concentration and that AlF4(-)-induced release of AA is abolished by BAPTA, an intracellular Ca2+ chelator, even in the presence of GF 109203X, a specific and potent PKC inhibitor. This compound also blocks the liberation of the secretory phospholipase A2 in the extracellular medium, indicating that this enzyme is not involved in the potentiation of arachidonic acid by PKC inhibitors. On the other hand, the latter effect is completely abolished by treatment of platelets with AACOCF3, a specific inhibitor of cytosolic phospholipase A2 (cPLA2). These observations indicate that cPLA2 is responsible for the AlF4(-)-induced release of arachidonic acid by a mechanism that is down-regulated by PKC.
Nucciarelli
F
F
Institute of Medical Biochemistry, University of Perugia, Italy.
Gresele
P
P
Nardicchi
V
V
Porcellati
S
S
Macchioni
L
L
Nenci
G G
GG
Goracci
G
G
D000535:Aluminum / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015536:Down-Regulation; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005461:Fluorine / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism*
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C081565:arachidonyltrifluoromethane; C053629:fluoroaluminum; D016718:Arachidonic Acid; D005461:Fluorine; D004533:Egtazic Acid; D000535:Aluminum; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C070515:bisindolylmaleimide I; D002118:Calcium