Conflicting results have been reported regarding the effect of thiopental o
n 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) B-2 formation, arachido
nic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+](i)
) were measured in the presence or absence of thiopental (30-300 muM). Plat
elet activation was induced by adenosine diphosphate (ADP, 0.5-15 muM), epi
nephrine (0.1-20 muM) arachidonic acid (0.5-1.5 mM), or (+)-9,11-epithia-11
,12-methano-TXA(2) (STA(2), 30-500 nM). Measurements of primary aggregation
were performed in the presence of indomethacin (10 muM). Low concentration
s of ADP and epinephrine, which did not induce secondary aggregation in a c
ontrol study, induced strong secondary aggregation in the presence of thiop
ental (greater than or equal to 100 muM). Thiopental (greater than or equal
to 100 muM) also increased the TXB2 formation induced by ADP and epinephri
ne. Thiopental (300 muM) increased ADP- and epinephrine-induced H-3-AA rele
ase. Thiopental (300 muM) also augmented the ADP- and epinephrine-induced i
ncreases in [Ca2+](i) in the presence of indomethacin. Thiopental appears t
o enhance ADP- and epinephrine-induced secondary platelet aggregation by in
creasing AA release during primary aggregation, possibly by the activation
of phospholipase A(2).