The effects of okadaic acid and calyculin A on thrombin induced platelet reaction.
Okadaic acid and calyculin A, specific and cell permeable inhibitors of protein phosphatase 1 and 2A, inhibited aggregation, secretion and delta [Ca++]i in thrombin stimulated platelets. The inhibitory effect of calyculin A (IC50: 3.6-4.8nM) was about two hundred times more potent than that of okadaic acid (IC50: 0.8-1.3 microM), which is consistent with the difference of the reported Ki values for protein phosphatase 1. These phosphatase inhibitors and PGI2 synergistically enhanced the phosphorylation of 50kDa protein (P50), which is solely related to the inhibition of platelet reaction. These results indicate that serine/threonine protein phosphatase 1 might play a role in platelet activation.
Murata
K
K
Department of Surgery II, Osaka University Medical School, Japan.
Sakon
M
M
Kambayashi
J
J
Yukawa
M
M
Ariyoshi
H
H
Shiba
E
E
Kawasaki
T
T
Kang
J
J
Mori
T
T
D000255:Adenosine Triphosphate / Q000032:analysis; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000032:analysis; D011464:Epoprostenol / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D054645:Protein Phosphatase 1; D013917:Thrombin / Q000494:pharmacology*
D004988:Ethers, Cyclic; D007476:Ionophores; D008387:Marine Toxins; D010080:Oxazoles; D010975:Platelet Aggregation Inhibitors; D019319:Okadaic Acid; C059041:calyculin A; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D013917:Thrombin; D002118:Calcium