Dissociation between secretion and protein phosphorylation in agonist-stimulated platelets; action of PCA-4230, a new antithrombotic drug.
We have studied the effects of PCA-4230, a new dihydropyridine derivative with antithrombotic activity, on the secretion of dense and alpha-granules from platelets and on the protein phosphorylation in platelets after stimulation by agonists. The drug prevented both dense and alpha-granule secretion evoked by thrombin, platelet-activating factor (PAF) and ionophore A23187, the former secretion being more sensitive than the latter one to the PCA-4230 action. These inhibitory effects on secretion processes did not correlate with the differential action of PCA-4230 on protein phosphorylation. Thus, the 40 kDa protein phosphorylation evoked by thrombin was potentiated whereas that elicited by ionophore A23187 was partially inhibited. The 20 kDa protein phosphorylation was practically insensitive to the drug action. These data, together with previous evidence reported by us on PCA-4230, lead us to suggest the existence of a common and critical step for platelet secretion evoked by agonists with different signal transduction pathways.
Departamento de Biología Molecular, Centro de Biología Molecular (CSIC-UAM), Madrid, Spain.
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Catalán
A M
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Martínez
M D
MD
Aragonés
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F
Hernández
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Garde
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Lombardía
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D001798:Blood Proteins / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology
D001798:Blood Proteins; D004095:Dihydropyridines; D005343:Fibrinolytic Agents; D010972:Platelet Activating Factor; C073664:PCA 4230; D000001:Calcimycin; D013917:Thrombin