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- W1965708783 abstract "During secondary aggregation, platelets release 5-hydroxytryptamine (5-HT) from their dense granule stores concurrent with arachidonic acid (AA) metabolism. To examine the hypothesis that released 5-HT has a modulatory effect on the metabolism of AA by platelets, we incubated nonaggregating washed human platelets with 5-HT in the presence of [ 3 H]AA. Stimulation with 10 −4 M 5-HT, followed by incubation with 3 μM AA and 1 μCi [ 3 H]AA for 5 min, resulted in a decrease in the formation of thromboxane B 2 (TxB 2 ) and 12-hydroxyheptadecatrienoic acid (HHT, P < 0.05). The same treatment conditions and stimulation with 10 −7 to 10 −4 M 5-HT resulted in an elevation of 12-hydroxyeicosatetraenoic acid (12-HETE) formation (P < 0.05). Treatment with the monoamine uptake inhibitor imipramine (20 μM) further increased the stimulation of 12-HETE formation observed in the presence of 10 −4 M 5-HT, suggesting that 5-HT may act at the platelet surface. A 5-HT 1A receptor agonist, 8-hydroxy-dipropylaminotetralin (DPAT, 10 −6 to 10 −4 M) stimulated the formation of platelet cyclooxygenase (CO) products, whereas (±)1-(2,5-dimethoxy-4-iodo phenyl)-amino propane hydrochloride (DOI, 10 −6 to 10 −4 M), a 5-HT 2 receptor agonist, had no significant effect on CO product formation. In addition, the 5-HT 2 receptor antagonist ketanserin (10 −7 M) did not block the changes in CO or lipoxygenase metabolism induced by 5-HT. Since both DOI and DPAT stimulated 12-HETE formation whereas ketanserin was unable to reverse the 5-HT-enhanced 12-HETE formation, it seems unlikely that the stimulation of a 5-HT 2 receptor is responsible for this action of 5-HT on platelets. We conclude that 5-HT depresses CO product formation while increasing 12-HETE formation through interaction with a platelet serotonergic binding site other than the 5-HT 2 receptor." @default.
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- W1965708783 date "1990-07-01" @default.
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- W1965708783 title "5-Hydroxytryptamine and the metabolism of arachidonic acid by the lipoxygenase and cyclooxygenase of washed human platelets" @default.
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- W1965708783 doi "https://doi.org/10.1016/0006-2952(90)90693-f" @default.
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