Concomitant activation of Gi protein-coupled receptor and protein kinase C or phospholipase C is required for platelet aggregation.
It has recently been suggested that the concomitant activation of two distinct G protein-coupled receptors (G(i) and G(q)) is essential for platelet aggregation: in fact, the thromboxane A2 synthetic agonist, U46619, which causes the selective activation of Gq, is not able to elicit fibrinogen receptor exposure unless ADP or epinephrine is present. In the present study we demonstrate that a direct Gq activation is not required for platelet aggregation and that the activation of an enzyme downstream of Gq, such as phospholipase C (PLC) or protein-kinase C (PKC), is sufficient for such a process. In fact, platelet aggregation occurred in response to the snake venom toxin convulxin, which activates the PLC isoform PLCgamma2 or to cytosolic PKC activator phorbol 12-myristate 13-acetate (PMA) provided a Gi protein-coupled receptor was activated by ADP or epinephrine. The evidence that the PKC inhibitor, Ro 31-8220 did not suppress platelet aggregation in response to convulxin plus ADP or epinephrine led us to conclude that PLC and PKC are both involved in platelet aggregation, although not concomitantly, provided a Gi protein-coupled receptor is activated.
Pulcinelli
F M
FM
Department of Experimental Medicine and Pathology, University of La Sapienza, Rome, Italy.
Ciampa
M T
MT
Favilla
M
M
Pignatelli
P
P
Riondino
S
S
Gazzaniga
P P
PP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D037181:Lectins, C-Type; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D002614:Chelating Agents; D003435:Crotalid Venoms; D007211:Indoles; D037181:Lectins, C-Type; D010975:Platelet Aggregation Inhibitors; C028890:convulxin; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; C064758:Ro 31-8220; D004837:Epinephrine