Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5-hydroxytryptamine

British Journal of Pharmacology
D J Boullin, R A O'Brien

Abstract

1. We have studied the mechanism of quinidine uptake by normal human blood platelets.2. Platelets in plasma or Krebs solution took up quinidine extremely rapidly, the maximal drug concentration ratio of platelet to medium being 24 to 1 after 1 minute.3. The effects of metabolic inhibitors on uptake were equivocal. Ouabain had no effect but iodoacetate and dinitrophenol were effective. However, as accumulation was not inhibited by low temperature, it was probably not energy dependent.4. Interactions between quinidine and 5-HT were also investigated.5. Quinidine blocked 5-HT uptake, but conversely, neither 5-HT itself nor 5-HT uptake inhibitors, such as cocaine, dexamphetamine, and desipramine interfered with quinidine accumulation.6. Electronmicrographs of platelets incubated with 10(-5), 10(-4) or 2 x 10(-3)M quinidine in Krebs solution for 2 h showed no changes at the lower concentrations, but gross ultastructural damage, including disintegration of the plasma membrane, at 2 x 10(-3)M.7. Further evidence for intracellular penetration was obtained because quinidine released endogenous 5-HT and ATP, and also (14)C-5-HT from loaded cells.8. We conclude that quinidine is taken up by the platelet by a passive process, unrelated to ...Continue Reading

References

Jul 1, 1968·Journal of Ultrastructure Research·O Behnke
Feb 1, 1966·The Journal of Pharmacy and Pharmacology·L Ahtee, M K Paasonen
Jul 1, 1968·The Journal of Pharmacy and Pharmacology·D J Boullin, R A O'Brien
Jan 1, 1968·Advances in Pharmacology·J P TranzerA Pletscher
Jan 1, 1969·British Journal of Pharmacology·D J Boullin, R A O'Brien
Sep 1, 1969·Proceedings of the Society for Experimental Biology and Medicine·J W Davis, S J Wilson
Dec 29, 1955·The Journal of Physiology·R M HARDISTY, R S STACEY
Mar 1, 1958·British Journal of Pharmacology and Chemotherapy·G V BORNR S STACEY
Jun 1, 1961·British Journal of Pharmacology and Chemotherapy·R S Stacey

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Citations

Jan 1, 1972·Naunyn-Schmiedeberg's Archives of Pharmacology·B LemmerH Grobecker
Dec 1, 1972·The Journal of Clinical Investigation·D Deykin, L J Hellerstein
Oct 1, 1982·The Journal of Pharmacy and Pharmacology·S FlemingerC D Marsden

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