Thrombosis and haemostasis, 2003-02, Vol.89 (2), p.310
2003
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- Autor(en) / Beteiligte
- Titel
- Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets
- Ist Teil von
- Thrombosis and haemostasis, 2003-02, Vol.89 (2), p.310
- Ort / Verlag
- Germany
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- P-selectin is rapidly translocated from platelet alpha-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 solicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0340-6245DOI: 10.1055/s-0037-1613448Titel-ID: cdi_pubmed_primary_12574812
- Format
- –
- Schlagworte
- Adenylyl Cyclases - drug effects, Adenylyl Cyclases - metabolism, Alkaloids - pharmacology, Blood Platelets - drug effects, Blood Platelets - enzymology, Blood Platelets - metabolism, Carbazoles, Cell Adhesion - drug effects, Cell Adhesion - physiology, Colforsin - pharmacology, Cyclic AMP - physiology, Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors, Cyclic AMP-Dependent Protein Kinases - physiology, Cyclic GMP - physiology, Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors, Cyclic GMP-Dependent Protein Kinases - physiology, Enzyme Activation - drug effects, Enzyme Inhibitors - pharmacology, Gene Expression Regulation - physiology, Humans, Indoles, Isoquinolines - pharmacology, Neutrophils - metabolism, P-Selectin - biosynthesis, P-Selectin - genetics, Phosphorylation, Platelet Activation - drug effects, Protein Processing, Post-Translational, Second Messenger Systems - physiology, Sulfonamides, Thrombin - pharmacology