title: Thiopental enhances human platelet aggregation by increasing arachidonic acid release.
abstract: Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30-300 microM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5-15 microM), epinephrine (0.1-20 microM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30-500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 microM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental (> or = 100 microM). Thiopental (> or = 100 microM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 microM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 microM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.
authors.affiliation: Department of Anesthesia, Kyoto University Hospital, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kitamura
authors.forename: H
authors.initials: H
authors.lastname: Hirakata
authors.forename: H
authors.initials: H
authors.lastname: Okuda
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Toda
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Hatano
authors.forename: N
authors.initials: N
authors.lastname: Urabe
authors.forename: K
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D016718:Arachidonic Acid / Q000097:blood*; D002118:Calcium / Q000097:blood; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D010974:Platelet Aggregation / Q000187:drug effects*; D013268:Stimulation, Chemical; D013874:Thiopental / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D018757:GABA Modulators; D007202:Indicators and Reagents; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013874:Thiopental; D002118:Calcium