Protein kinase C activation is not a key step in ADP-mediated exposure of fibrinogen receptors on human platelets

• Published in: FEBS letters 1995-05, Vol.364 (1), p.87-90
• Main Authors: Pulcinelli, Fabio M., Ashby, Barrie, Gazzaniga, Pier Paolo, Daniel, James L.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; ADP; Blood Platelets - drug effects; Blood Platelets - enzymology; Blood Proteins - metabolism; Calcium - metabolism; Enzyme Activation; Fibrinogen - metabolism; Humans; Indoles - pharmacology; Phosphoproteins; Phosphorylation - drug effects; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation - physiology; Platelet Aggregation Inhibitors - pharmacology; Platelet Membrane Glycoproteins - metabolism; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Thromboxane A2
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00352-A

A selective inhibitor of protein kinase C (PKC), Ro 31-8220, blocks pleckstrin (P47) phosphorylation in platelets activated with either ADP, ADP plus synthetic thromboxane agonist U46619 and ADP plus U46619 plus epinephrine, while inducing a weak inhibition of platelet aggregation, and no significant effect on the fibrinogen binding. In platelets activated by U46619 alone, P47 phosphorylation, platelet aggregation, fibrinogen binding and serotonin release are all inhibited by Ro 318220. In the presence of an ADP scavenger system, U46619 induces pleckstrin phosphorylation, serotonin release and calcium mobilization but not platelet aggregation and fibrinogen binding, unless epinephrine is added. In conclusion: (1) PKC activation is required for ADP secretion; (2) ADP or epinephrine are essential for fibrinogen receptor exposure induced by U46619; (3) fibrinogen receptor exposure induced by ADP is independent of activation of PKC.