The effects of adriamycin and adriamycin complexes with transitional metals on Ca(2+)-dependent K+ channels of human erythrocytes.
The influence of adriamycin (ADR) and ADR complexes with transitional metals Fe2+, Cu2+ and Co2+ on Ca(2+)-dependent K+ channels of human erythrocytes was investigated. We show that the anthracycline moiety of ADR increases Ca(2+)-dependent K+ efflux from erythrocytes, induced by low concentrations of propranolol, while the whole molecule of ADR has not any effect on Ca(2+)-dependent K+ channels, induced by propranolol or A23187 and on Pb(2+)-dependent K+ efflux. Ethidium bromide, verapamil and trifluoroperazine inhibited Ca(2+)-dependent K+ efflux, induced by high doses of propranolol. The anthracycline moiety of ADR is able to abolish blocking effect of ethidium bromide and verapamil, but does not influence the blocking effect of trifluoroperazine. We further show that ADR complexes with Fe2+, Cu2+ and Co2+ are potent inhibitors of Ca(2+)-dependent K+ efflux, induced by propranolol, but not of Pb(2+)-dependent K+ efflux. On the contrary, ADR-Fe3+ complex activates K(+)-permeability of human red blood cell. It is suggested that opposite effects of anthracycline moiety of ADR and ADR complexes with transitional metals on Ca(2+)-dependent K+ channels, induced by propranolol is due to their influence on the pathways of Ca2+ transport into cells, rather than their action directly on K+ channels.
Davtyan
T K
TK
Laboratory of Immunology, Ministry of Health, Yerevan, Armenia.
Gyulkhandanyan
A V
AV
Gambarov
S S
SS
Avanessian
L A
LA
Alexanyan
Y T
YT
D002118:Calcium / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004317:Doxorubicin / Q000494:pharmacology*; D004563:Electrochemistry; D004912:Erythrocytes / Q000187:drug effects*; D004996:Ethidium / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019216:Metals, Heavy / Q000378:metabolism*; D008954:Models, Biological; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D019216:Metals, Heavy; D009942:Organometallic Compounds; D015221:Potassium Channels; C053170:doxorubicin-cobalt(II) complex; C053169:doxorubicin-copper(II) complex; C041415:doxorubicin-iron complex; D014268:Trifluoperazine; D004317:Doxorubicin; D011433:Propranolol; D014700:Verapamil; D004996:Ethidium; D011188:Potassium; D002118:Calcium