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Thromb Haemost 2003; 89(02): 310-317
DOI: 10.1055/s-0037-1613448
Platelets and Blood Cells
Schattauer GmbH

Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets

Danielle Libersan
1   Montreal Heart Institute, Research Center, Montreal, Quebec, Canada
,
Guy Rousseau
2   Hôpital du Sacré-Cœur, Research Center, Montreal, Quebec, Canada
,
Yahye Merhi
1   Montreal Heart Institute, Research Center, Montreal, Quebec, Canada
› Author Affiliations
Further Information

Publication History

Received 22 June 2002

Accepted after revision 03 September 2002

Publication Date:
07 December 2017 (online)

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Summary

P-selectin is rapidly translocated from platelet α-granules following activation. Intracellular cyclic AMP (cAMP) is a potent inhibitory pathway that results in global downregulation of platelet activation. While cAMP-dependent protein kinase (PKA) has long been considered as the main mediator of cAMP-dependent effects, no study has yet evaluated its effect on P-selectin expression in human platelets. Pretreatment of thrombin-stimulated platelets with forskolin resulted in a concentration-dependent inhibition of P-selectin expression that correlated with adenylyl cyclase activity. Inhibition of PKA with H-89 reversed cAMP-induced inhibition of P-selectin while cGMP-dependent protein kinase (PKG) inhibition with KT5823 significantly potentiated cAMP-dependent inhibition of P-selectin. Similar results were also observed in a platelet/neutrophil binding assay. In conclusion, cAMP-induced inhibition of P-selectin expression is, in large part, mediated through activation of PKA. PKG appears to be sollicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation.

Keywords

Platelets - P-selectin - cAMP - PKA - PKG
 

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