Summary
Palytoxin increases the permeability of human erythrocytes and their resealed ghosts. To elucidate its mode of action the activation by ATP and Ca2+, the inhibition by ouabain, and the changes in permselectivity have been studied:
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1.
Depletion of cells from ATP considerably depresses their sensitivity towards palytoxin. Ouabain prevents the actions of the toxin, however, with different inhibition characteristics in normal and depleted cells.
The concentration of palytoxin required to raise the K+ permeability is higher in ghosts than in erythrocytes. The sensitivity is restored by incorporating ATP which can be partially substituted by ADP and GTP but not by AMP, Pi, β-γ-methylene adenosine 5′-triphosphate or the chromium (III) complex of ATP.
Ouabain inhibits the K+ release from resealed ghosts in the presence as well as absence of ATP. Ouabain also inhibits the palytoxin-triggered Na+ and choline efflux into Na+ medium, as well as the Na+, K+ and choline efflux into choline medium. Phosphate promotes the inhibitory action of ouabain. Incorporated vanadate or Mg2+ do not change the sensitivity of ghosts toward palytoxin.
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2.
External calcium down to 10 μM potentiates the action of palytoxin in ghosts resealed with or without ATP. In contrast to calcium ionophore A23187, palytoxin does not raise the influx of Ca2+.
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3.
Palytoxin triggers the formation of small pores in resealed ghosts. The efflux into Na+ medium decreases in the order K+≧Na+>[3H]choline≫[14C]inositol>[14C]sucrose, [3H]inulin≅0.
Our data suggest that palytoxin, once bound to erythrocyte membranes, transforms the sodium pump, or its functional vicinity, into a pore allowing the passive transport of small ions. This process is assisted by ATP from inside whereas Ca2+ promotes from the outside the efficacy of palytoxin.
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Part of this work will be included into the thesis of H.-J. Hessler
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Chhatwal, G.S., Hessler, HJ. & Habermann, E. The action of palytoxin on erythrocytes and resealed ghosts. Naunyn-Schmiedeberg's Arch. Pharmacol. 323, 261–268 (1983). https://doi.org/10.1007/BF00497672
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DOI: https://doi.org/10.1007/BF00497672