Increases in aggregation by and uptake of 5-hydroxytryptamine with platelets from rabbits treated with chlorpromazine.

1 Citrated platelet-rich plasma was prepared from New Zealand white rabbits before, during and after administration of chlorpromazine (2 mg/kg) intramuscularly once daily for 3 to 4 weeks. 2 In these plasmas, the velocity of platelet aggregation by 5-hydroxytryptamine (5-HT) added at 1, 3 and 10 microM increased greatly, beginning 3 to 4 days after the start of chlorpromazine injections and lasting for a similar period after they were terminated. The increase had two maxima, the first after 6 to 10 days and the second after 17 to 24 days. Chlorpromazine treatment did not affect aggregation by adenosine diphosphate (ADP). 3 The uptake of 5-HT by rabbit platelets was very fast and linear for less than 10 s. In platelets from untreated rabbits the uptake had a Km of 0.35 +/- 0.08 microM and a Vmax of 39.8 +/- 6.1 pmol 10(-8) platelets 10(-1) (n = 5). 4 In platelets from rabbits injected with chlorpromazine (see (2) above) both kinetic constants increased significantly, the Km to 0.88 +/- 0.08 microM and the Vmax to 67.8 +/- 5.5 pmol. 10(-8) platelets. 10(-1) s (n = 9).