Thromb Haemost 1997; 78(02): 919-925
DOI: 10.1055/s-0038-1657652
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Schattauer GmbH Stuttgart

Different Requirement of Intracellular Calcium and Protein Kinase C for Arachidonic Acid Release and Serotonin Secretion in Cathepsin G-activated Platelets

Serenella Rotondo
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Virgilio Evangelista
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Stefano Manarini
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Giovanni de Gaetano
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
,
Chiara Cerletti
“Giulio Bizzozero” Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
› Author Affiliations
Further Information

Publication History

Received 08 1996

Accepted after revision 19 March 1997

Publication Date:
12 July 2018 (online)

Summary

Previous studies have shown that platelet stimulation with cathepsin G rapidly results in cytoplasmic calcium ([Ca2+]j) increase and activation of protein kinase C (PKC). To elucidate the relationship between these two biochemical events and their relative contribution to the regulation of platelet response to cathepsin G, arachidonic acid (AA) release and serotonin (5HT) secretion were studied. Platelets made Ca2+- depleted and -permeable by treatment with A23187 were compared to intact platelets to better dissociate calcium changes from other receptor- stimulated events. AA release elicited by cathepsin G in intact platelets was prevented by the Ca2+ chelator BAPTA; in Ca2+-depleted, -permeable platelets AA was released in direct response to added Ca2+ and was not increased by simultaneous stimulation with cathepsin G. In intact platelets, PKC inhibition by Ro 31-8220 or PKC induction with PMA either enhanced or reduced, respectively, cathepsin G-induced AA release. Both BAPTA and Ro 31-8220 prevented 5HT secretion from intact platelets; however, in Ca2+-depleted, -permeable platelets, cathepsin G was able to evoke 5HT secretion and p47 phosphorylation independently of [Ca2+]j increase, both effects being hampered by Ro 31-8220. Ca2+ and PKC therefore regulate PLA2 activity and 5HT secretion in cathepsin G-stimulated platelets in a different manner: the former is mainly triggered by [Ca2+]j increase, while PKC represents the major factor in determining dense granule secretion.