Metabolism of arachidonic acid by macaque platelets. Implications for studies on atherosclerosis.
The metabolism of [1-14C]arachidonic acid [( 1-14C]AA) by washed platelets from macaques and human subjects was investigated. The results were as follows: At substrate levels of 1 microM, similar amounts of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), and thromboxane A2 (TXA2), measured as thromboxane B2 (TXB2), were produced from [1-14C]AA by platelets from rhesus, Celebes black, and cynomolgus macaques and humans. An increase in the AA concentration from 1 microM to 20 microM decreased the TXB2: PGD2 ratio (aggregator: antiaggregator) from greater than 5 to less than 2 in all series. In the human series, the ratio decrease was due to an increase in PGD2 production; in the macaque series, PGD2 production increased and TXB2 production decreased. Under basal conditions and at 1 microM AA concentrations, the amounts of prostaglandins and thromboxanes produced by platelets from male and female rhesus macaques were the same. An increase in substrate concentration from 1 microM to 20 microM AA decreased TXB2 production and increased PGD2 production to the same extent in platelets from male and female rhesus macaques. Imidazole increased prostaglandin production and decreased TXB2 production by platelets from both male and female rhesus macaques. The TXB2: PGD2 ratios were reduced below 1.5; there was no difference between the ratios in the two series. In the presence of 1 mM imidazole, greater amounts of prostaglandins and thromboxanes were produced in the male than in the female series. These data indicate that macaque's platelets are a suitable model for the study of AA metabolism in human platelets.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001161:Arteriosclerosis / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D006801:Humans; D008251:Macaca / Q000097:blood*; D008297:Male; D015230:Prostaglandin D2; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011457:Prostaglandins D / Q000097:blood; D011458:Prostaglandins E / Q000097:blood; D011460:Prostaglandins F / Q000097:blood; D012737:Sex Factors; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D015230:Prostaglandin D2