Platelet 5-Hydroxytryptamine Increases with Platelet Age in Dogs

Summary

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.

• References

• 1 Vanhoutte PM, Cohen RA. The elusory role of serotonin in vascular function and disease. Biochem Pharmacol 1983; 32: 3671-4
• 2 Benedict CR, Mathew B, Rex KA, Cartwright Jr J, Sordahl LA. Correlation of plasma serotonin changes with platelet aggregation in an in vivo dog model of spontaneous occlusive coronary thrombus formation. Circ Res 1986; 73: 58-67
• 3 Gaddum JH, Giarman NJ. Preliminary studies on the biosynthesis of 5-hydroxytryptamine. Br J Pharmacol 1956; 11: 88-92
• 4 Morrissey JJ, Walker MN, Lovenberg W. The absence of tryptophan hydroxylase activity in blood platelets. Proc Soc Exp Biol Med 1977; 154: 496-9
• 5 Tranzer JP, Da Prada M, Pletscher A. Storage of 5-hydroxytryptamine in megakaryocytes. J Cell Biol 1972; 52: 191-7
• 6 Lenehan T, Omer LMO, Kenny M, Lambe R, Darragh A. The effect of multiple rising doses of Ro 11-2465 (serotonin uptake inhibitor) on serotonin content of human platelets. Psychopharmacology 1981; 74: 1-3
• 7 Pletscher A, Da Prada M. The organelles storing 5-hydroxytryptamine in blood platelets. In: Biochemistry and Pharmacology of Platelets. Ciba Foundation Symposium 35.. Elsevier, Amsterdam: 1975. pp 261-79
• 8 Stoltz JF. Uptake and storage of serotonin by platelets. In: Serotonin and the Cardiovascular System. Vanhoutte PM. (ed) Raven Press, New York: 1985. pp 37-42
• 9 Corash L, Costa JL, Shafer B, Donlon JA, Murphy D. Heterogeneity of human whole blood platelet subpopulations. III. Density-dependent differences in subcellular constituents. Blood 1984; 64: 185-93
• 10 Reimers H-J, Kinlough-Rathbone RL, Cazenave J-P, Senyi AF, Hirsh J, Packham MA, Mustard JF. In vitro and in vivo functions of thrombin-treated platelets. Thromb Haemostas 1976; 35: 151-66
• 11 Osim EE, Wyllie JH. Loss of 5-hydroxytryptamine from mammalian circulating labelled platelets. J Physiol 1983; 340: 77-90
• 12 Reimers H-J, Allen DJ, Feuerstein IA, Mustard JF. Transport and storage of serotonin by thrombin-treated platelets. J Cell Biol 1975; 65: 359-72
• 13 Hagen I, Bjerrum OJ, Solum NO. Characterization of human platelet proteins solubilized with Triton X-100 and examined by crossed immunoelectrophoresis. Reference patterns of extracts from whole platelets and isolated membranes. Eur J Biochem 1979; 99: 9-22
• 14 Steinbuch M, Audran R. The isolation of IgG from mammalian sera with the aid of caprylic acid. Arch Biochem Biophys 1969; 134: 279-84
• 15 Philp RB. In vitro tests of platelet function and platelet inhibitory drugs. In: Methods of Testing Proposed Antithrombotic Drugs. Philp RB. (ed) CRC Press, Boca Raton, CA: 1981. pp 129-69
• 16 Arias Elenes N, Ewald RA, Crosby WH. The reservoir function of the spleen and its relation to postsplenectomy anemia in the dog. Blood 1964; 24: 299-304
• 17 Mezzano D, Aranda E, Foradori A, Rodriguez S, Lira P. Kinetics of platelet density subpopulations in splenectomized mongrel dogs. Am J Hematol 1984; 17: 373-82
• 18 Murphy EA, Francis ME. The estimation of blood platelet survival. II. The multiple hit model. Thromb Diathes Haemorrh 1971; 25: 53-80
• 19 Keyfitz N. Interrelationships of demographic variables in stable populations. In: Introduction to the Mathematics of Population.. Addison-Wesley, Reading, MA: 1968. pp 170-94
• 20 Kraytman M. A simple method for induction of acute thrombocytopenia. J Lab Clin Lab 1969; 73: 350-4
• 21 Mezzano D, Hwang KL, Aster RH. Characteristics of total platelet populations and of platelets isolated in platelet-rich plasma. Transfusion 1982; 22: 197-202
• 22 Von Behrens WE. Mediterranean macrothrombocytopenia. Blood 1975; 46: 199-208
• 23 Drummond AH, Gordon JL. Rapid, sensitive microassay for platelet 5-HT. Thromb Diathes Haemorrh 1974; 31: 366-7
• 24 Mezzano D, Aranda E, Rodriguez S. Foradori A, Lira P. Increase in density and accumulation of serotonin by human aging platelets. Am J Hematol 1984; 17: 11-21
• 25 Gernsheimer T, Stratton G, Ballem PJ, Slichter SJ. Mechanisms of response to treatment in autoimmune thrombocytopenic purpura. N Engl J Med 1989; 320: 974-80
• 26 Weiss HJ, Rosove MH, Lages BA, Kaplan KL. Acquired storage pool deficiency with increased platelet-associated IgG. Am J Med 1980; 69: 711-7
• 27 Zahavi J, Marder VJ. Acquired "Storage Pool Disease" of platelets associated with circulating antiplatelet antibodies. Am J Med 1974; 56: 883-90
• 28 Colman RW, Schreiber AD. Effect of heterologous antibody on human platelets. Blood 1976; 48: 119-31
• 29 Mezzano D, Aranda E, Foradori A. Comparative study of size, total protein, fibrinogen and 5-HT content of human and canine platelets density subpopulations. Thromb Haemostas 1986; 56: 288-92
• 30 Steinberg H, Das DK. Competition between platelets and lung for 5-hydroxytryptamine uptake. Exp Lung Res 1980; 1: 121-30
• 31 Tyce GM. Biochemistry of serotonin. In: Serotonin and the Cardiovascular System.. Vanhoutte PM. (ed) Raven Press, New York: 1985. pp 1-13
• 32 Brammer GL, McGuire MT, Raleigh MJ. Vervet monkey (Cercopithecus aethiops sabaeus) whole blood serotonin level is determined by platelet uptake sites. Life Sci 1987; 41: 1539-46