Epinephrine potentiates calcium mobilization and activation of protein kinases in platelets stimulated by ADP through a mechanism unrelated to phospholipase C.
ADP, added to suspensions of aspirinized 32P-prelabelled washed platelets, induced reversible platelet aggregation, the rapid elevation of cytosolic Ca2+ (maximum at 2 s), 20 kDa myosin light chain phosphorylation (maximum faster than 3 s), 40 kDa protein phosphorylation (maximum at 3-10 s) and phosphatidic acid formation (maximum at 30 s). Prior addition of epinephrine potentiated platelet aggregation, cytosolic Ca2(+)-elevation, 20 and 40 kDa protein phosphorylation evoked by ADP, but it did not enhance phosphatidic acid formation induced by ADP. The potentiating effect of epinephrine on aggregation, cytosolic Ca2(+)-increase and 20 and 40 kDa protein phosphorylation induced by ADP was also observed in the presence of EGTA. Ethylisopropylamiloride, an inhibitor of Na+/H(+)-exchange, did not affect the potentiation of ADP-induced platelet aggregation by epinephrine. We conclude that epinephrine primes platelets to increase Ca2(+)-influx and Ca2(+)-mobilization in response to ADP. The potentiation of cytosolic Ca2(+)-elevation by epinephrine leads to further stimulation of myosin light chain phosphorylation and protein kinase C activation and ultimately to enhanced platelet aggregation. These effects of epinephrine do not seem to take place at the level of phospholipase C.
Olbrich
C
C
Medizinische Klinik Innenstadt Universitaet Muenchen, F.R.G.
Aepfelbacher
M
M
Siess
W
W
D000244:Adenosine Diphosphate / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D004789:Enzyme Activation; D004837:Epinephrine / Q000502:physiology*; D006801:Humans; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000502:physiology*; D011494:Protein Kinases / Q000097:blood*; D010738:Type C Phospholipases / Q000502:physiology
D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D000244:Adenosine Diphosphate; D011494:Protein Kinases; D010738:Type C Phospholipases; D002118:Calcium; D004837:Epinephrine