ACCUMULATION OF 5-HYDROXYTRYPTAMINE BY AGING PLATELETS - STUDIES IN AMODEL OF SUPPRESSED THROMBOPOIESIS IN DOGS

Thrombocytopenia was induced in healthy, male mongrel dogs by intramus cular injection of a single dose of estradiol valerate (1 mg/kg). A st eady, almost linear decay of the blood platelet count starting about d ay 6 post-estradiol and attaining a mean value of 14 x 10(3) platelets /mu l one week later was observed. Thrombocytopenia is explained mainl y by suppression of thrombocytopoiesis, as established by two independ ent ways: 1. Megakaryocytes in the bone marrow were markedly reduced. 2. Kinetic studies with In-111 labeled autologous platelets revealed a nearly linear decay of the radioactivity and mean survival times with in 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-hydroxytryptam ine (5-HT) increased from a basal value of 130 +/- 30 ng/10(8) platele ts (platelet count of 351 +/- 53 x 10(3) platelets/mu l) to 343 +/- 10 0 ng/10(8) platelets eleven days latter, when the platelet count dropp ed to 32 +/- 18 x 10(3) platelets/mu l. 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 in dicate that aging platelets accumulate 5-HT, probably by a sustained e xposure to the monoamine in plasma, confirming previous observations b ased on models in which thrombopenia was induced by immune and mechani cal means.