Differential effects of 12-O-tetradecanoylphorbol 13-acetate on platelet responses to various agonists in the presence and absence of extracellular Ca2

In the presence of 1 mM extracellular Ca2+ (Ca2+o), incubation of washed, quin 2 loaded platelets with a low concentration (1 nM) of 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited platelet shape change, aggregation, ATP secretion and cytosolic calcium (Ca2+i) fluxes in response to thrombin, pl...

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Bibliographic Details
Published in:	Thrombosis research Vol. 44; no. 2; p. 185
Main Authors:	Powling, M J, Hardisty, R M
Format:	Journal Article
Language:	English
Published:	United States 15-10-1986
Subjects:	Adenosine Triphosphate - metabolism Aminoquinolines Blood Platelets - drug effects Blood Platelets - metabolism Calcium - metabolism Calcium - pharmacology Cytosol - enzymology Cytosol - metabolism Humans Platelet Activating Factor - pharmacology Platelet Aggregation - drug effects Prostaglandin Endoperoxides, Synthetic - pharmacology Tetradecanoylphorbol Acetate - pharmacology Thrombin - pharmacology Vasopressins - pharmacology
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Summary:	In the presence of 1 mM extracellular Ca2+ (Ca2+o), incubation of washed, quin 2 loaded platelets with a low concentration (1 nM) of 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited platelet shape change, aggregation, ATP secretion and cytosolic calcium (Ca2+i) fluxes in response to thrombin, platelet activating factor (PAF), adenosine diphosphate (ADP), vasopressin (VP) and the thromboxane mimetic U46619, but potentiated platelet activation induced by the calcium ionophores, A23187 and ionomycin, the Ca2+ flux remaining unaltered. In the presence of less than 100 nM Ca2+o, TPA again inhibited shape change but potentiated ATP secretion induced by all agonists, even those in which the cytosolic calcium flux was inhibited. Addition of TPA 30 seconds after a low dose of agonist, sufficient to elevate [Ca2+i] to about 250 nM without causing aggregation, induced substantial aggregation and dense granule secretion without affecting Ca2+ flux. These results confirm that very slight elevation of [Ca2+i] above resting levels greatly enhances the effect of low concentrations of TPA, and suggest that protein kinase C activation may exert a feedback inhibition of receptor-mediated shape change, aggregation, ATP secretion and Ca2+ mobilization.
ISSN:	0049-3848