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. 1978 Feb;62(2):219–226. doi: 10.1111/j.1476-5381.1978.tb08449.x

5-Hydroxytryptamine and dopamine transport by rat and human blood platelets

JL Gordon, HJ Olverman
PMCID: PMC1667818  PMID: 623937

Abstract

1 Uptake of 5-hydroxytryptamine (5-HT) by rat platelets in plasma was very rapid and diffusion did not contribute significantly at substrate concentrations that did not saturate the active transport.

2 Under conditions which allowed measurement of initial rates of uptake, kinetic analysis revealed a high affinity uptake mechanism for 5-HT (Km = 0.7 μM).

3 Uptake of dopamine was relatively slow and involved a lower affinity (Km = 70 μM) active transport process. Diffusion contributed significantly at concentrations that did not saturate the active transport.

4 5-HT competitively inhibited uptake of dopamine, and vice versa; Ki values for both amines were similar to their respective Km values for uptake.

5 Chlorimipramine, desmethylimipramine and benztropine were tested as uptake inhibitors. Each was equipotent against 5-HT and dopamine, although the absolute potency of the drugs varied greatly. Chlorimipramine was the most potent (Ki## 100 nM), and kinetic analysis revealed that the inhibition was competitive against both 5-HT and dopamine.

6 Similar results were obtained in studies with human platelets: Km values for 5-HT and dopamine were about 1 μM and 100 μM respectively. Activity profiles of inhibitors were also similar: each compound tested was equipotent against 5-HT and dopamine, and the two amines each competitively inhibited uptake of the other.

7 We conclude that dopamine is actively transported by platelets via the 5-HT uptake mechanism, but with a much lower affinity. There is no high-affinity dopamine-specific mechanism corresponding to that in the corpus striatum. Consequently although platelets may be valid models of transport in 5-hydroxytryptaminergic neurones, they should not be regarded as models for the dopamine transport mechanism found in dopaminergic neurones.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrams W. B., Solomon H. M. The human platelet as a pharmacologic model for the adrenergic neuron. The uptake and release of norepinephrine. Clin Pharmacol Ther. 1969 Sep-Oct;10(5):702–709. doi: 10.1002/cpt1969105702. [DOI] [PubMed] [Google Scholar]
  2. BORN G. V., GILLSON R. E. Studies on the uptake of 5-hydroxytryptamine by blood platelets. J Physiol. 1959 Jun 11;146(3):472–491. doi: 10.1113/jphysiol.1959.sp006206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balfour D. J. Effects of nicotine on the uptake and retention of 14C-noradrenaline and 14C-5-hydroxytryptamine by rat brain homogenates. Eur J Pharmacol. 1973 Jul;23(1):19–26. doi: 10.1016/0014-2999(73)90240-9. [DOI] [PubMed] [Google Scholar]
  4. Boullin D. J., Green A. R., Grimes R. P. Proceedings: Human blood platelet aggregation induced by dopamine, 5-hydroxyptrypamine and analogues. J Physiol. 1975 Nov;252(2):46P–47P. [PubMed] [Google Scholar]
  5. Boullin D. J., O'Brien R. A. Accumulation of dopamine by blood platelets from normal subjects and parkinsonian patients under treatment with L-DOPA. Br J Pharmacol. 1970 Aug;39(4):779–788. doi: 10.1111/j.1476-5381.1970.tb09904.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DIXON M. The determination of enzyme inhibitor constants. Biochem J. 1953 Aug;55(1):170–171. doi: 10.1042/bj0550170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Da Prada M., Pletscher A. Differential uptake of biogenic amines by isolated 5-hydroxytryptamine organelles of blood platelets. Life Sci. 1969 Jan 1;8(1):65–72. doi: 10.1016/0024-3205(69)90294-x. [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. Drummond A. H., Gordon J. L. Specific binding sites for 5-hydroxytryptamine on rat blood platelets. Biochem J. 1975 Jul;150(1):129–132. doi: 10.1042/bj1500129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Drummond A. H., Gordon J. L. Uptake of 5-hydroxytryptamine by rat blood platelets and its inhibition by adenosine 5'-diphosphate. Br J Pharmacol. 1976 Apr;56(4):417–421. doi: 10.1111/j.1476-5381.1976.tb07452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FUKS Z., LANMAN R. C., SCHANKER L. S. ON THE MEMBRANE EFFECTS OF CHLORPROMAZINE: UPTAKE OF BIOLOGIC AMINES BY THE BLOOD PLATELET AND RED CELL. Int J Neuropharmacol. 1964 Dec;3:623–633. doi: 10.1016/0028-3908(64)90087-5. [DOI] [PubMed] [Google Scholar]
  12. Horn A. S., Coyle J. T., Snyder S. H. Catecholamine uptake by synaptosomes from rat brain. Structure-activity relationships of drugs with differential effects on dopamine and norepinephrine neurons. Mol Pharmacol. 1971 Jan;7(1):66–80. [PubMed] [Google Scholar]
  13. 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]
  14. Shaskan E. G., Snyder S. H. Kinetics of serotonin accumulation into slices from rat brain: relationship to catecholamine uptake. J Pharmacol Exp Ther. 1970 Nov;175(2):404–418. [PubMed] [Google Scholar]
  15. Sneddon J. M. Blood platelets as a model for monoamine-containing neurones. Prog Neurobiol. 1973;1(2):151–198. doi: 10.1016/0301-0082(73)90019-1. [DOI] [PubMed] [Google Scholar]
  16. Snyder S. H., Coyle J. T. Regional differences in H3-norepinephrine and H3-dopamine uptake into rat brain homogenates. J Pharmacol Exp Ther. 1969 Jan;165(1):78–86. [PubMed] [Google Scholar]
  17. Solomon H. M., Spirt N. M., Abrams W. B. The accumulation and metabolism of dopamine by the human platelet. Clin Pharmacol Ther. 1970 Nov-Dec;11(6):838–845. doi: 10.1002/cpt1970116838. [DOI] [PubMed] [Google Scholar]
  18. Todrick A., Tait A. C. The inhibition of human platelet 5-hydroxytryptamine uptake by tricyclic antidepressive drugs. The relation between structure and potency. J Pharm Pharmacol. 1969 Nov;21(11):751–762. doi: 10.1111/j.2042-7158.1969.tb08164.x. [DOI] [PubMed] [Google Scholar]
  19. Trenchard A., Turner P., Pare C. M., Hills M. The effects of protriptyline and clomipramine in vitro on the uptake of 5-hydroxytryptamine and dopamine in human platelet-rich plasma. Psychopharmacologia. 1975 Jul 23;43(1):89–93. doi: 10.1007/BF00437621. [DOI] [PubMed] [Google Scholar]
  20. Tuomisto J. A new modification for studying 5-HT uptake by blood platelets: a re-evaluation of tricyclic antidepressants as uptake inhibitors. J Pharm Pharmacol. 1974 Feb;26(2):92–100. doi: 10.1111/j.2042-7158.1974.tb09231.x. [DOI] [PubMed] [Google Scholar]
  21. Wielosz M., Salmona M., de Gaetano G., Garattini S. Uptake of 14C-5-hydroxytryptamine by human and rat platelets and its pharmacological inhibition. A comparative kinetic analysis. Naunyn Schmiedebergs Arch Pharmacol. 1976 Dec;296(1):59–65. doi: 10.1007/BF00498840. [DOI] [PubMed] [Google Scholar]
  22. Wielosz M., de Gaetano G., Garattini S. Improved method for evaluating the inhibition of [14C]5-Hydroxytryptamine uptake by rat platelets. J Pharm Pharmacol. 1976 Sep;28(9):717–718. doi: 10.1111/j.2042-7158.1976.tb02846.x. [DOI] [PubMed] [Google Scholar]

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