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. 1974 Aug;54(2):421–432. doi: 10.1172/JCI107778

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

Harvey J Weiss 1,2, Thomas B Tschopp 1,2, John Rogers 1,2, Harvey Brand 1,2
PMCID: PMC301570  PMID: 4847252

Abstract

Platelets in patients with storage pool disease are markedly deficient in a nonmetabolic (storage) pool of ADP that is important in platelet aggregation. They are also deficient in ATP, although to a lesser degree. In seven patients with this disorder, including one with albinism, platelet 5-hydroxytryptamine (5-HT) levels were reduced in proportion to the reduction in ATP (r = 0.94). Their platelets show diminished capacity to absorb [14C]5-HT, and the type of defect was similar to that produced in normal platelets by reserpine, a drug known to inhibit the uptake of 5-HT by the platelet dense granules. Storage pool-deficient platelets also converted more [3H]5-HT to [3H]5-hydroxyindoleacetic acid than did normal platelets, and the platelets in one of two patients studied contained increased amounts of 5-HT metabolites. The above findings, together with those reported previously, support the conclusion that the capacity of the dense granules (which may be either diminished or functionally abnormal) for storing 5-HT is decreased in storage pool disease; as a result, the 5-HT that enters the platelet may be more exposed to monoamine oxidases present on mitochondrial membranes. This diminished storage capacity (for 5-HT) may also explain why preincubating platelet-rich plasma with 5-HT for 45 min without stirring inhibits subsequent platelet aggregation by 5-HT to a greater degree in patients with storage pool disease than in normal subjects. The latter finding is also consistent with the theory that the aggregation of platelets by 5-HT is mediated by the same receptors on the plasma membrane that are involved in its uptake. The diminished release of platelet-bound [14C]5-HT by collagen that we found in these patients, as well as findings in previous studies, suggests that the release reaction may also be abnormal in storage pool disease.

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Selected References

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  1. BORN G. V., INGRAM G. I., STACEY R. S. The relationship between 5-hydroxytryptamine and adenosine triphosphate in blood platelets. Br J Pharmacol Chemother. 1958 Mar;13(1):62–64. doi: 10.1111/j.1476-5381.1958.tb00191.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baumgartner H. R., Born G. V. Effects of 5-hydroxytryptamine on platelet aggregation. Nature. 1968 Apr 13;218(5137):137–141. doi: 10.1038/218137a0. [DOI] [PubMed] [Google Scholar]
  3. Boullin D. J., O'Brien R. A. Abnormalities of 5-hydroxytryptamine uptake and binding by blood platelets from children with Down's syndrome. J Physiol. 1971 Jan;212(2):287–297. doi: 10.1113/jphysiol.1971.sp009325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CONTRACTOR S. F. THE ESTIMATION OF 5-HYDROXYTRYPTAMINE IN HUMAN BLOOD. Biochem Pharmacol. 1964 Sep;13:1351–1357. doi: 10.1016/0006-2952(64)90235-7. [DOI] [PubMed] [Google Scholar]
  5. CROSTI P. F., LUCCHELLI P. E. An easy method to determine the serotonin content of human platelets. J Clin Pathol. 1962 Mar;15:191–193. doi: 10.1136/jcp.15.2.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Da Prada M., Bartholini G., Pletscher A. Effect of monoamine liberators on the metabolism of 5-hydroxytryptamine in blood platelets. Biochem Pharmacol. 1965 Dec;14(12):1721–1726. doi: 10.1016/0006-2952(65)90261-3. [DOI] [PubMed] [Google Scholar]
  7. Da Prada M., Pletscher A. Different localization of reserpine and tyramine within the 5-hydroxytryptamine organelles of blood platelets. Experientia. 1969 Sep 15;25(9):923–924. doi: 10.1007/BF01898064. [DOI] [PubMed] [Google Scholar]
  8. Da Prada M., Pletscher A. Isolated 5-hydroxytryptamine organelles of rabbit blood platelets: physiological properties and drug-induced changes. Br J Pharmacol. 1968 Nov;34(3):591–597. doi: 10.1111/j.1476-5381.1968.tb08487.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Da Prada M., Pletscher A., Tranzer J. P., Knuchel H. Action of reserpine on subcellular 5-hydroxytryptamine organelles of blood platelets. Life Sci. 1968 May 1;7(9):477–480. doi: 10.1016/0024-3205(68)90050-7. [DOI] [PubMed] [Google Scholar]
  10. Da Prada M., Pletscher A., Tranzer J. P., Knuchel H. Subcellular localization of 5-hydroxytryptamine and histamine in blood platelets. Nature. 1967 Dec 30;216(5122):1315–1317. doi: 10.1038/2161315a0. [DOI] [PubMed] [Google Scholar]
  11. Da Prada M., Pletscher A., Tranzer J. P. Storage of ATP and 5-hydroxytryptamine in blood platelets of guinea-pigs. J Physiol. 1971 Sep;217(3):679–688. doi: 10.1113/jphysiol.1971.sp009593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Davis R. B., White J. G. Localization of 5-hydroxytryptamine in blood platelets: an autoradiographic and ultrastructural study. Br J Haematol. 1968 Jul;15(1):93–99. doi: 10.1111/j.1365-2141.1968.tb01515.x. [DOI] [PubMed] [Google Scholar]
  13. HARDISTY R. M., STACEY R. S. Platelet 5-hydroxytryptamine (HT) in disorders of the blood. Br J Haematol. 1957 Jul;3(3):292–298. doi: 10.1111/j.1365-2141.1957.tb05799.x. [DOI] [PubMed] [Google Scholar]
  14. Hardisty R. M., Mills D. C., Ketsa-Ard K. The platelet defect associated with albumism. Br J Haematol. 1972 Dec;23(6):679–692. doi: 10.1111/j.1365-2141.1972.tb03483.x. [DOI] [PubMed] [Google Scholar]
  15. Holmsen H., Day H. J. Adenine nucleotides and platelet function. Ser Haematol. 1971;4(1):28–58. [PubMed] [Google Scholar]
  16. Holmsen H., Day H. J., Storm E. Adenine nucleotide metabolism of blood platelets. VI. Subcellular localization of nucleotide pools with different functions in the platelet release reaction. Biochim Biophys Acta. 1969 Aug 20;186(2):254–266. doi: 10.1016/0005-2787(69)90003-3. [DOI] [PubMed] [Google Scholar]
  17. Holmsen H., Day H. J., Stormorken H. The blood platelet release reaction. Scand J Haematol Suppl. 1969;8:3–26. [PubMed] [Google Scholar]
  18. Holmsen H., Ostvold A. C., Day H. J. Behaviour of endogenous and newly absorbed serotonin in the platelet release reaction. Biochem Pharmacol. 1973 Oct 15;22(20):2599–2608. doi: 10.1016/0006-2952(73)90068-3. [DOI] [PubMed] [Google Scholar]
  19. Holmsen H., Storm E., Day H. J. Determination of ATP and ADP in blood platelets: a modification of the firefly luciferase assay for plasma. Anal Biochem. 1972 Apr;46(2):489–501. doi: 10.1016/0003-2697(72)90323-5. [DOI] [PubMed] [Google Scholar]
  20. Holmsen H., Weiss H. J. Further evidence for a deficient storage pool of adenine nucleotides in platelets from some patients with thrombocytopathia--"storage pool disease". Blood. 1972 Feb;39(2):197–209. [PubMed] [Google Scholar]
  21. Holmsen H., Weiss H. J. Hereditary defect in the platelet release reaction caused by a deficiency in the storage pool of platelet adenine nucleotides. Br J Haematol. 1970 Nov;19(5):643–649. doi: 10.1111/j.1365-2141.1970.tb01648.x. [DOI] [PubMed] [Google Scholar]
  22. Jérome H., Kamoun P. Anomalie de la captaion de la sérotonine par les plaquettes sanguines des sujets trisomiques 21. I. Etude des caractéristiques générales de la captation. Bull Soc Chim Biol (Paris) 1968;50(4):907–921. [PubMed] [Google Scholar]
  23. Klein D. C., Ntides A. Thin-layer chromatographic separation of pineal gland derivatives of serotonin-14C. Anal Biochem. 1969 Oct 1;31(1):480–483. doi: 10.1016/0003-2697(69)90290-5. [DOI] [PubMed] [Google Scholar]
  24. Logan L. J., Rapaport S. I., Maher I. Albinism and abnormal platelet function. N Engl J Med. 1971 Jun 17;284(24):1340–1345. doi: 10.1056/NEJM197106172842402. [DOI] [PubMed] [Google Scholar]
  25. MITCHELL J. R., SHARP A. A. PLATELET CLUMPING IN VITRO. Br J Haematol. 1964 Jan;10:78–93. doi: 10.1111/j.1365-2141.1964.tb00681.x. [DOI] [PubMed] [Google Scholar]
  26. Maurer H. M., Wolff J. A., Buckingham S., Spielvogel A. R. "Impotent" platelets in albinos with prolonged bleeding times. Blood. 1972 Apr;39(4):490–499. [PubMed] [Google Scholar]
  27. Michal F. D-receptor for serotonin on blood platelets. Nature. 1969 Mar 29;221(5187):1253–1254. doi: 10.1038/2211253a0. [DOI] [PubMed] [Google Scholar]
  28. Paasonen M. K., Airaksinen M. M. Metabolism of 5-hydroxytryptamine in blood platelets of rabbit. Ann Med Exp Biol Fenn. 1965;43(4):236–240. [PubMed] [Google Scholar]
  29. Paasonen M. K., Solatunturi E. Monoamine oxidase in mammalian blood platelets. Ann Med Exp Biol Fenn. 1965;43(2):98–100. [PubMed] [Google Scholar]
  30. Pletscher A., Da Prada M., Berneis K. H., Tranzer J. P. New aspects on the storage of 5-hydroxytryptamine in blood platelets. Experientia. 1971 Sep 15;27(9):993–1002. doi: 10.1007/BF02138839. [DOI] [PubMed] [Google Scholar]
  31. Pletscher A. Metabolism, transfer and storage of 5-hydroxytryptamine in blood platelets. Br J Pharmacol Chemother. 1968 Jan;32(1):1–16. doi: 10.1111/j.1476-5381.1968.tb00423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pletscher A., Tranzer J. P. Action of reserpine and imipramine on intracellular storage of 5-hydroxytryptamine in blood platelets. Experientia. 1967 Apr 15;23(4):289–291. doi: 10.1007/BF02135693. [DOI] [PubMed] [Google Scholar]
  33. RAND M., REID G. Source of 'serotonin' in serum. Nature. 1951 Sep 1;168(4270):385–385. doi: 10.1038/168385b0. [DOI] [PubMed] [Google Scholar]
  34. Safrit H. F., Weiss H. J., Phillips G. B. The phospholipid and fatty acid composition of platelets in patients with primary defects of platelet function. Lipids. 1972 Jan;7(1):60–67. doi: 10.1007/BF02531271. [DOI] [PubMed] [Google Scholar]
  35. Sankar D. V. Biogenic amine uptake by blood platelets and RBC in childhood scizophrenia. Acta Paedopsychiatr. 1970 Nov;37(6):174–182. [PubMed] [Google Scholar]
  36. Smith I., Rider L. J., Lerner R. P. Chromatography of amino acids, indoles and imidazoles on thin layers of avicel and cellulose and on paper. J Chromatogr. 1967 Feb;26(2):449–455. doi: 10.1016/s0021-9673(01)98902-2. [DOI] [PubMed] [Google Scholar]
  37. Smith J. B., Ingerman C., Kocsis J. J., Silver M. J. Formation of prostaglandins during the aggregation of human blood platelets. J Clin Invest. 1973 Apr;52(4):965–969. doi: 10.1172/JCI107262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tschopp T. B., Zucker M. B. Hereditary defect in platelet function in rats. Blood. 1972 Aug;40(2):217–226. [PubMed] [Google Scholar]
  39. Weiss H. J. Abnormalities in platelet function due to defects in the release reaction. Ann N Y Acad Sci. 1972 Oct 27;201:161–173. doi: 10.1111/j.1749-6632.1972.tb16297.x. [DOI] [PubMed] [Google Scholar]
  40. Weiss H. J., Aledort L. M., Kochwa S. The effect of salicylates on the hemostatic properties of platelets in man. J Clin Invest. 1968 Sep;47(9):2169–2180. doi: 10.1172/JCI105903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weiss H. J., Ames R. P. Ultrastructural findings in storage pool disease and aspirin-like defects of platelets. Am J Pathol. 1973 Jun;71(3):447–466. [PMC free article] [PubMed] [Google Scholar]
  42. Weiss H. J., Chervenick P. A., Zalusky R., Factor A. A familialdefect in platelet function associated with imapired release of adenosine diphosphate. N Engl J Med. 1969 Dec 4;281(23):1264–1270. doi: 10.1056/NEJM196912042812303. [DOI] [PubMed] [Google Scholar]
  43. Weiss H. J. Platelet aggregation, adhesion and adenosine diphosphate release in thrombopathia (platelet factor 3 deficiency). A comparison with Glanzmann's thrombasthenia and von Willebrand's disease. Am J Med. 1967 Oct;43(4):570–578. doi: 10.1016/0002-9343(67)90180-5. [DOI] [PubMed] [Google Scholar]
  44. Weiss H. J., Rogers J. Platelet factor 4 in platelet disorders--storage location and the requirement of endogenous ADP for its release. Proc Soc Exp Biol Med. 1973 Jan;142(1):30–35. doi: 10.3181/00379727-142-36951. [DOI] [PubMed] [Google Scholar]
  45. Weiss H. J., Rogers J. Thrombocytopathia due to abnormalities in platelet release reaction--studies on six unrelated patients. Blood. 1972 Feb;39(2):187–196. [PubMed] [Google Scholar]
  46. White J. G., Edson J. R., Desnick S. J., Witkop C. J., Jr Studies of platelets in a variant of the Hermansky-Pudlak syndrome. Am J Pathol. 1971 May;63(2):319–332. [PMC free article] [PubMed] [Google Scholar]
  47. White J. G. The dense bodies of human platelets: inherent electron opacity of the serotonin storage particles. Blood. 1969 Apr;33(4):598–606. [PubMed] [Google Scholar]
  48. Willis A. L., Weiss H. J. A congenital defect in platelet prostaglandin production associated with impaired hemostasis in storage pool disease. Prostaglandins. 1973 Dec;4(6):783–794. doi: 10.1016/0090-6980(73)90114-7. [DOI] [PubMed] [Google Scholar]
  49. Zucker M. B., Peterson J. Inhibition of adenosine diphosphate-induced secondary aggregation and other platelet functions by acetylsalicylic acid ingestion. Proc Soc Exp Biol Med. 1968 Feb;127(2):547–551. doi: 10.3181/00379727-127-32737. [DOI] [PubMed] [Google Scholar]

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