Thiopental enhances human platelet aggregation by increasing arachidonic acid release.
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.
Kitamura
R
R
Department of Anesthesia, Kyoto University Hospital, Japan.
Hirakata
H
H
Okuda
H
H
Sato
M
M
Toda
H
H
Nakamura
K
K
Hatano
Y
Y
Urabe
N
N
Fukuda
K
K
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
D018757:GABA Modulators; D007202:Indicators and Reagents; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013874:Thiopental; D002118:Calcium