Thromb Haemost 1977; 37(01): 062-072
DOI: 10.1055/s-0038-1649202
Original Article
Schattauer GmbH

Induction of the Platelet Release Reaction by 1.3-Dimethyl-5-Aminoadamantane, a New Adamantane Derivative

Uta Haacke
1   Institut für Physiologische Chemie II der Philipps-Universität Marburg/Lahn, Fed. Rep. Germany
,
Wolfgang Wesemann
1   Institut für Physiologische Chemie II der Philipps-Universität Marburg/Lahn, Fed. Rep. Germany
› Author Affiliations
Further Information

Publication History

Received 25 September 1975

Accepted 08 September 1976

Publication Date:
03 July 2018 (online)

Summary

The amantadine derivative 1.3-dimethyl-5-aminoadamantane, D 145, induces in high concentrations of 2–10 mM the release reaction. Adenine nucleotides and 5-hydroxytryptamine (5-HT) are liberated to the same extent and in the same ratio as found after thrombin-induced release. The time course of release is very slow; maximal release is reached in 15–20 min. The process is temperature-dependent and dependent on energy derived from glycolysis and oxidative phosphorylation. Extracellular Ca++ does not promote the release process. D 145, in accordance with the mother-substance amantadine, inhibits 5-HT uptake non-competitively, KI = 0.15 mM. In concentrations of 0.1–1 mM D 145 triggers only the liberation of 5-HT, adenine nucleotides are not liberated. The ADP induced platelet aggregation is completely inhibited after preincubation with a 1 mM solution of D 145.

 
  • References

  • 1 Bergmeyer H.U, Bernt E. UV-Test mit Pyruvat und NADH. In: Bergmeyer H.U. (ed.) Methoden der enzymatischen Analyse, Band I 1970. Verlag Chemie; Weinheim.: p. 533
  • 2 Berneis K.H, Pletscher A, Da Prada M. Phase separation in solutions of noradrenaline and adenosine triphosphate: influence of bivalent cations and drugs. British Journal of Pharmacology 1970; 39: 382
  • 3 Bogdanski D.F, Pletscher A, Brodie B.B, Udenfriend S. Identification and assay of serotonin in brain. Journal of Pharmacology and Experimental Therapeutics 1956; 117: 82
  • 4 Born G.V.R, Cross M.J. The aggregation of blood platelets. 1963. Journal of Physiology; London: 168 178
  • 5 Bray G.A. A simple efficient liquid scintillator for counting aqueous solutions in a liquid scintillation counter. Analytical Biochemistry 1960; 1: 279
  • 6 Costa J.L, Reese T.S. Serotonin storage in platelets: Estimation of storage – packet size. Science 1974; 183: 537
  • 7 Da Prada M, Pletscher A. Isolated 5-hydroxytryptamine organelles of rabbit blood platelets: physiological properties and drug induced changes. British Journal of Pharmacology 1968; 34: 591
  • 8 Da Prada M, Pletscher A, Tranzer J.P, Knuchel H. Action of reserpine on subcellular 5-hydroxytryptamine organelles of blood platelets. Life Sciences 1968; 7: 477
  • 9 Da Prada M, Pletscher A. Mechanisms of 5-hydroxytryptamine storage in subcellular organelles of blood platelets. In: Costa E, Gessa G.L, Sandler M. (eds.) Serotonin – New Vistas. Advances in Biochemical Psychopharmacology, Vol. 10 1974. Raven Press; New York.: p. 311
  • 10 Dixon M. The determination of enzyme inhibitor constants. Biochemical Journal 1953; 55: 170
  • 11 Gaintner J.R, Jackson D.P, Maynert E.W. The action of thrombin on platelet 5-hydroxytryptamine. Bulletin of the Johns Hopkins Hospital 1962; 111: 185
  • 12 Glusa Erika, Barthel W, Markwardt F. The influence of benzamidine derivatives on human platelet function. Thrombosis et Diathesis Haemorrhagica 1974; 31: 172
  • 13 Hohorst H.-J. L – (+) Lactat. Bestimmung mit Lactat-Dehydrogenase und NAD. In: Bergmeyer H.U. (ed.) Methoden der enzymatischen Analyse, B and II 1970. Weinheim.; Verlag Chemie: p. 1425
  • 14 Holmsen H, Holmsen I, Bernhardsen A. Microdetermination of adenosine diphosphate and adenosine triphosphate in plasma with the firefly luciferase system. Analytical Biochemistry 1966; 17: 456
  • 15 Holmsen H, Day H.J, Storm Eva. Adenine nucleotide metabolism of blood platelets: VI. Subcellular localization of nucleotide pools with different functions in the platelet release reaction. Biochimica et Biophysica Acta 1969; 186: 254
  • 16 Holmsen H, Day H.J. The selectivity of the thrombin-induced platelet release reaction: subcellular localization of released and retained constituents. Journal of Laboratory and Clinical Medicine 1970; 75: 840
  • 17 Holmsen H. The platelet: its membrane, physiology and biochemistry. In: O’Brien J.R. (ed.) Clinics in Haematology, Vol. 1, 2 1972. W. B. Saunders; London, Philadelphia, Toronto.: p. 235
  • 18 Holmsen H, Storm Eva, Day H.J. Determination of ATP and ADP in blood platelets. Analytical Biochemistry 1972; 46: 489
  • 19 Hunter A, Downs C.E. The inhibition of arginase by amino acids. Journal of Biological Chemistry 1945; 157: 427
  • 20 Kuhar M.J, Roth R.H, Aghajanian G.K. Synaptosomes from forebrain of rats with midbrain raphe lesions: selective reduction of serotonin uptake. Journal of Pharmacology and Experimental Therapeutics 1972; 181: 36
  • 21 Lemmer B. Effects of amantadine and amphetamine on serotonin uptake and release by human blood platelets. European Journal of Pharmacology 1973; 21: 183
  • 22 Lineweaver H, Burk D. The determination of enzyme dissociation constants. Journal of the American Chemical Society 1934; 56: 658
  • 23 Mills D.C.B, Robb I.A, Roberts G.C.K. The release of nucleotides, 5-hydroxytryptamine and enzymes from human blood platelets during aggregation. 1968. 195 Journal of Physiology; London: 715
  • 24 Mürer E.H, Day H.J, Lieberman J.E. Metabolic aspects of the secretion of stored com-pounts from blood platelets: III. Effects of NaF on washed platelets. Biochimica et Biophysica Acta 1974; 362: 266
  • 25 O’Brien J.R. Platelet aggregation, Part II. Some results from a new method of study. Journal of Clinical Pathology 1962; 15: 446
  • 26 Pletscher A, Burkard W.P, Tranzer J.P, Gey K.F. Two sites of 5-hydroxytryptamine uptake in blood platelets. Life Sciences 1967; 6: 273
  • 27 Pletscher A, Tranzer J.P. Action of reserpine and Imipramine on intracellular storage of 5-hydroxytryptamine in blood platelets. Experientia 1967; 23: 289
  • 28 Schwab R.S, England S.C, Poskanzer D.C, Young R.R. Amantadine in the treatment of Parkinson’s disease. Journal of the American Medical Association 1969; 208: 1168
  • 29 Stacey R.S. Uptake of 5-hydroxytryptamine by platelets. British Journal of Pharmacology 1961; 16: 284
  • 30 Waller H.D, Löhr G.W, Grignani F, Gross R. Über den Energiestoffwechsel normaler menschlicher Thrombozyten. Thrombosis et Diathesis Haemorrhagica 1959; 3: 520
  • 31 Wesemann W, Schollmeyer J.D. Biochemical effects of adamantanamines, a new class of drugs with antiparkinson activity. Agents and Actions 1973; 3: 195