Platelet responses promoted by the activation of protein kinase C or the increase of cytosolic Ca2+ are potentiated by adrenaline. Effects of cAMP and staurosporine.
We studied the action of the alpha 2 adrenergic agonist adrenaline on the platelet responses evoked by the activation of protein kinase C or by the ionophore induced increase of cytosolic Ca2+. Both the phorbol ester and ionomycin-induced aggregation are strongly potentiated by adrenaline which per se does not behave as an activating agonist. The potentiation by adrenaline is observed both when added before and after the aggregating agent; in the latter case the effect increases on increasing the delay of adrenaline addition. Adrenaline also reverses the inhibition by cAMP of the PMA (or ionomycin) induced aggregation. It also has a strong potentiating effect (over 100%) on the phorbol ester induced ATP secretion and a weaker effect on the secretion induced by ionomycin. The effect on secretion is visible only when adrenaline is added prior to the stimulus. The inhibition by cAMP of the PMA or ionomycin induced secretion is also counteracted by adrenaline. In no case adrenaline modifies the pattern of platelet phosphoproteins. Ionomycin induces some platelet aggregation also in the presence of the protein kinase inhibitor staurosporine; also this phosphoprotein independent aggregation is strongly stimulated by adrenaline.
Zoccarato
F
F
Department of Biological Chemistry, C.N.R. Unit for the Study of Mitochondrial Physiology, University of Padova, Italy.
Ruzzene
M
M
Cavallini
L
L
Doni
M G
MG
Francesconi
M A
MA
Deana
R
R
Alexandre
A
A
D000470:Alkaloids / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D019311:Staurosporine; D010738:Type C Phospholipases / Q000187:drug effects
D000470:Alkaloids; D015759:Ionomycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019311:Staurosporine; D002118:Calcium; D004837:Epinephrine