Summary
Beta-adrenergic blocking agents inhibit serotonin uptake by human blood platelets; in addition they induce release of the previously accumulated amine in vitro. Propranolol was the most active drug, followed by alprenolol, Kl 255, Kö 592, INPEA, oxprenolol, pindolol, Kö 1366, practolol, and sotalol. Kinetic analysis revealed a mixed type of inhibition of serotonin uptake. A significant correlation between these parameters and the lipid solubilities of the respective drugs was found. In contrast to the active serotonin uptake labelled β-sympatholytics were accumulated by the platelets passively, i. e. independently of temperature and of time of incubation. The degree of accumulation by human blood platelets and human erythrocyte ghosts was again correlated with the hydrophobicity of the compounds. Therefore, it is concluded that these effects of β-adrenergic blocking agents are mainly unspecific in nature, depending on the lipid solubility of the drugs, and leading to conformational changes within the membranes. This assumption is supported by the electron microscopical findings in human platelets, indicating ultrastructural changes and cell lysis.
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References
Abrams, W. B., Solomon, H. M.: The human platelet as a pharmacological model for the adrenergic neuron. The uptake and release of norepinephrine. Clin. Pharmacol. Ther. 10, 702–709 (1969).
Ambs, E., Bahr, G. F., Zeitler, E.: Trockengewichtsbestimmungen von Thrombocyten mit Hilfe des Elektronenmikroskopes. Z. ges. exp. Med. 154, 187–197 (1971).
Born, G. V. R., Hornykiewicz, O., Stafford, A.: The uptake of adrenaline and noradrenaline by blood platelets of the pig. Brit. J. Pharmacol. 13, 411–414 (1958).
Born, G. V. R., Smith, J. B.: Uptake, metabolism and release of 3H-adrenaline by human platelets. Brit. J. Pharmacol. 39, 765–778 (1970).
Boullin, D. J., McMahon, E. M., O'Brien, R. A.: Uptake of dopamine by platelets in vivo. Brit. J. Pharmacol. 40, 522–523 (1970).
Boullin, D. J., O'Brien, R. A.: Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5-hydroxytryptamine. Brit. J. Pharmacol. 42, 114–126 (1971).
Dixon, M., Webb, E. C.: Enzymes, 2nd edition 1965, pp. 315–331. London: Longmans, Green and Co. Ltd. 1965.
Dodge, I. T., Mitchell, C., Hanahan, D.: The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch. Biochem. 100, 119–130 (1963).
Dollery, C. T., Paterson, J. W., Conolly, M. E.: Clinical pharmacology of beta-receptor-blocking drugs. Clin. Pharmacol. Ther. 10, 765–799 (1969).
Fitzgerald, J. D.: Perspectives in adrenergic beta-receptor-blockade. Clin. Pharmacol. Ther. 10, 292–306 (1969).
Grobecker, H., Lemmer, B.: Influence of coronary dilators on the uptake of serotonin by human platelets and adrenaline by chromaffine granules. Experientia (Basel) 27, 299–301 (1971).
Grobecker, H., Lemmer, B., Hellenbrecht, D., Wiethold, G.: The influence of prenylamine, verapamil, propranolol. d,l-INPEA, and LB-46 on serotonin uptake by human platelets in vitro and in vivo. Naunyn-Schmiedebergs Arch. Pharmak., Suppl. 270, R 46 (1971).
Hellenbrecht, D., Wiethold, G., Grobecker, H.: Influence of β-adrenergic blocking agents on the excitibility of frog nerve and myocardium. Naunyn-Schmiedeberg's Arch. Pharmacol., Suppl. 274, R 50 (1972).
Langslet, A.: Membrane stabilization and cardiac effects of d,l-propranolol, d-propranolol and chlorpromazine. Europ. J. Pharmacol. 13, 6–14 (1970).
Lemmer, B.: Effects of amantadine and amphetamine on serotonin uptake and release by human blood platelets. Europ. J. Pharmacol. (in press) (1972).
Lemmer, B., Wiethold, G., Bak, I. J., Hellenbrecht, D., Grobecker, H.: Human blood platelets and erythrocytes as cellular models for investigation of membrane active drugs, 2nd Int. Symp. on Metabolism and Membrane Permeability of Erythrocytes, Thrombocytes and Leucocytes, Vienna, June 10–16, 1972, Abstr. p. 49.
Lineweaver, H., Burk, D.: The determination of enzyme dissociation constants. J. Amer. chem. Soc. 56, 658–666 (1934).
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. biol. Chem. 193, 265–275 (1951).
May, B., Menkens, I., Westermann, E.: Freisetzung von Serotonin und Histamin aus Thrombocyten durch aliphatische und aromatische Amine. Naunyn-Schmiedebergs Arch. Pharmak. 265, 24–48 (1969).
Nakao, K., Angrist, A. A.: Membrane surface specialization of blood platelets and mega-karyocyte. Nature (Lond.) 217, 960–961 (1968).
Seeman, P. M.: Membrane stabilization by drugs: transquilizers, steroids, and anesthetics. Int. Rev. Neurobiol. 9, 145–221 (1966).
Wiethold, G., Lemmer, B., Hellenbrecht, D., Grobecker, H., Palm, D.: Conformational changes in membranes by β-sympatholytic agents. Naunyn-Schmiedeberg's Arch. Pharmacol., Suppl. 274, R125 (1972).
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Lemmer, B., Wiethold, G., Hellenbrecht, D. et al. Human blood platelets as cellular models for investigation of membrane active drugs: Beta-adrenergic blocking agents. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 299–313 (1972). https://doi.org/10.1007/BF00500058
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DOI: https://doi.org/10.1007/BF00500058