[Blocking with phorbol ester, a protein kinase C activator, of receptor-dependent platelet calcium channels].
The regulation of receptor-operated calcium channels of human platelets by phospholipid-dependent, Ca2+- and diacylglycerol-activated protein kinase C was studied. In order to induce the activation of endogenous protein kinase C, a cell-penetrable structural diacylglycerol analog, 4 beta-phorbol 12 beta-myristate-13 alpha-acetate (FMA), was used. Using two independent approaches, i. e., the fluorescent probe for Ca2+, quin-2, and 45Ca2+ absorption technique, it was demonstrated that FMA (10(-10) - 10(-8) g/ml) blocks Ca2+ influx into the platelets induced by aggregation factors, e. g., ADP, vasopressin, platelet activating factor, thrombin and thromboxane A2 receptor agonist U46619. The half-maximum inhibition of the receptor-sensitive influx of Ca2+ was observed at (3-6) X 10(-10) g/ml of FMA. Under physiological conditions, protein kinase C is activated with an increase in Ca2+ concentration in the cytoplasm in the presence of diacylglycerol. Since the above-mentioned inducers besides Ca2+ influx stimulate diacylglycerol synthesis, it was assumed that the activation of protein kinase C triggers a negative feedback mechanism which blocks the receptor-operated calcium channels.
P V
PV
Avdonin
I P
IP
Altukhova
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010704:Phorbols / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011493:Protein Kinase C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D005456:Fluorescent Dyes; D007473:Ion Channels; D010704:Phorbols; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium
Blokirovanie aktivatorom proteinkinazy C, forbolovym éfirom, retseptorzavisimykh kal'tsievykh kanalov trombotsitov.