High concentrations of arachidonic acid induce platelet aggregation and serotonin release independent of prostaglandin endoperoxides and thromboxane A2.
We examined platelet aggregation and serotonin release, induced by less than 60 micro M arachidonic acid, using washed platelet suspensions in the absence of albumin. The concentration of arachidonic acid used did not cause platelet lysis. Platelet responses induced by less than 20 micro M arachidonic acid were inhibited by aspirin, whereas those induced by above 30 micro M arachidonic acid were not inhibited, even by both aspirin and 5,8,11,14-eicosatetraynoic acid. Although phosphatidic acid and 1,2-diacylglycerol increased after the addition of arachidonic acid in aspirin-treated platelets, the amounts were not parallel to platelet aggregation. Oleic, linoleic and linolenic acids also induced platelet responses, while palmitic, stearic and arachidic acids did not. EDTA, dibutyryl cyclic AMP, apyrase and creatine phosphate/creatine phosphokinase brought about almost the same effects in platelet responses induced by the unsaturated fatty acids, other than arachidonic acid, as those induced by 40 micro M arachidonic acid. These results suggest that the mechanism of the actions of more than 30 micro M arachidonic acid on platelets is the same as that of the other unsaturated fatty acids and is independent of prostaglandin endoperoxides, thromboxane A2 and, perhaps, phosphatidic acid and 1,2-diacylglycerol.
Hashimoto
Y
Y
Naito
C
C
Kume
S
S
Kato
H
H
Watanabe
T
T
Kawamura
M
M
Teramoto
T
T
Oka
H
H
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000418:Albumins; D001081:Apyrase / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D003470:Culture Media; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D010712:Phosphatidic Acids / Q000378:metabolism; D010725:Phosphocreatine / Q000494:pharmacology; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013928:Thromboxane A2 / Q000494:pharmacology
D000418:Albumins; D001095:Arachidonic Acids; D003470:Culture Media; D004075:Diglycerides; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D010712:Phosphatidic Acids; D011449:Prostaglandin Endoperoxides; D010725:Phosphocreatine; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; D003994:Bucladesine; D004492:Edetic Acid; D001081:Apyrase; D001241:Aspirin