Accumulation of 5-Hydroxytryptamine by Aging Platelets: Studies in a Model of Suppressed Thrombopoiesis in Dogs

Summary Thrombocytopenia was induced in healthy, male mongrel dogs by intramuscular injection of a single dose of estradiol valerate (1 mg/kg). A steady, almost linear decay of the blood platelet count starting about day 6 post-estradiol and attaining a mean value of 14 × 103 platelets/pi one week later was observed. Thrombocytopenia is explained mainly by suppression- of thrombocytopoiesis, as established by two independent ways: 1. Megakaryocytes in the bone marrow were markedly reduced. 2. Kinetic studies with 11‘In labeled autologous platelets revealed a nearly linear decay of the radioactivity and mean survival times within the expected range. The progressive reduction in the platelet count is associated with an increase in the mean age of the platelets still circulating. Following estradiol injection, platelet 5-hydroxytryptamine (5-HT) increased from a basal value of 130 ± 30 ng/108 platelets (platelet count of 351 ± 53 × 103 platelets/p.1) to 343 ± 100 ng/108platelets eleven days latter, when the platelet count dropped to 32 ± 18 × 103 platelets/pi No significant changes in the number or affinity of the 5-HT uptake receptors could be demonstrated in platelets exposed in vitro and in vivo to estradiol. Our results indicate that aging platelets accumulate 5-HT, probably by a sustained exposure to the monoamine in plasma, confirming previous observations based on models in which thrombopenia was induced by immune and mechanical means.