Correlation Between Noradrenaline Fluxes, Metabolism and Compartmentalisation in Human Platelets

Summary

(³H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.

Keywords

Platelets - Noradrenaline - Storage - Metabolism - Fluxes

• References

• 1 Gordon JL, Olverman HJ. 5-hydroxytryptamine and dopamine transport by rat and human blood platelets. Br J Pharmacol 1978; 62: 215-226
• 2 Rudnick G, Fishkes H, Nelson PJ, Schuldiner S. Evidence for two distinct serotonin transport systems in platelets. J Biol Chem 1980; 255: 3638-3641
• 3 Pletscher A, Da Prada M. The organelles storing 5-hydroxy-tryptamine in blood platelets. In: Biochemistry and Pharmacology of Platelets. Ciba Found Sympos 35 Amsterdam – Oxford – New York, Elsevier Excerpta Medica North Holland: 1975: 261-279
• 4 Wilkins JA, Greenewalt JW, Huang L. Transport of 5-hydroxytryptamine by dense granules from porcine platelets. J Biol Chem 1978; 253: 6260-6265
• 5 von Pusch I, Wesemann W. Biochemical and autoradiographic studies on the intracellular distribution of 5-hydroxytryptamine and adenine in human blood platelets. Eur J Cell Biol 1979; 19: 11-18
• 6 Costa JL, Murphy DL, Kafka MS. Demonstration and evaluation of apparent cytoplasmic and vesicular serotonin compartments in human platelets. Biochem Pharmacol 1977; 26: 517-521
• 7 Born GVR, Smith JB. Uptake, metabolism and release of [³H] adrenaline by human platelets. Br J Pharmacol 1970; 39: 765-778
• 8 Costa JL, Murphy DL, Reveille J. Evaluation of the uptake of various amines into storage vesicles of intact human platelets. Br J Pharmacol 1977; 61: 223-228
• 9 Da Prada M, Picotti GB. Content and subcellular localization of catecholamines and 5-hydroxytryptamine in human and animal blood platelets: monoamine distribution between platelets and plasma. Br J Pharmacol 1978; 65: 653-662
• 10 Da Prada M, Picotti GB, Kettler R, Launay JM. Serotonin, histamine, catecholamines, normetanephrine and octopamine in blood platelets. In: Platelets: Cellular response mechanisms and their biological significance. Rotman A, Meyer FA, Gitler C, Silberberg A. (eds.), John Wiley and Sons Ltd; Chichester, New York, Brisbane, Toronto, A Wiley, Intersdence Publication: 1980: 277-288
• 11 Mattiasson I, Mattiasson B, Hood B. The efflux rate of norepinephrine from platelets and its relation to blood pressure. Life Sci 1979; 24: 2265-2272
• 12 Le Quan-Bui KH, Elghozi JL, Devynck MA, Meyer P. Early changes in noradrenalin content of some brain nuclei in spontaneous hypertensive rats. Clin Sei Mol Med 1980; 59 (Suppl. 00) 243-245
• 13 Hart RF, Rensker KJ, Nelson EB, Roth JA. Localization and characterization of phenol sulfotransferase in human platelets. Life Sci 1979; 24: 125-130
• 14 Rein G, Glover V, Sandler M. Sulphate conjugation of biologically active monoamines and their metabolites by human platelet phenol-sulfotransferase. Clin Chim Acta 1981; 111: 247-256
• 15 Marshall EF, Campbell IC. A method for the determination of platelet and plasma monoamine oxidase in whole blood. Biochem Pharmacol 1977; 26: 353-354
• 16 Schick PK, McKean ML. Serotonin binding in human platelets. Biochem Pharmacol 1979; 28: 2667-2670
• 17 Talvenheimo J, Nelson PJ, Rudnick G. Mechanism of imipramine inhibition of platelet 5-hydroxytryptamine transport. J Biol Chem 1979; 254: 4631-4635
• 18 Costa JL, Silber SA, Murphy DL. Effect of reserpine and imipramine on vesicular serotonin uptake and storage in intact human platelets. Life Sci 1977; 21: 181-188
• 19 Reimers HJ, Packham MA, Cazenave JP, Mustard JF. Effect of reserpine on adenosine uptake and metabolism and subcellular transport of platelet adenosine triphosphate in washed rabbit platelets. Biochem Pharmacol 1977; 26: 1657-1665
• 20 Enna SJ, Da Prada M, Pletscher A. Subcellular distribution of reserpine in blood platelets: evidence for multiple pools. J. Pharmacol Exp Ther 1974; 191: 164-171
• 21 Weiss HJ, Witte LD, Kaplan KL, Lages BA, Chernoff A, Nossel HL, Goodman DS, Baumgartner HR. Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in α-granules platelet factor 4, β thromboglobulin and platelet derived growth factor. Blood 1979; 54: 1296-1319
• 22 Rao AK, Niewiarowski S, Murphy S. Acquired granular pool defect in stored platelets. Blood 1981; 57: 203-208