Davtyan T K, Gyulkhandanyan A V, Gambarov S S, Avanessian L A, Alexanyan Y T
Laboratory of Immunology, Ministry of Health, Yerevan, Armenia.
Biochim Biophys Acta. 1996 Oct 17;1297(2):182-90. doi: 10.1016/s0167-4838(96)00091-x.
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.
研究了阿霉素（ADR）以及ADR与过渡金属Fe2+、Cu2+和Co2+形成的复合物对人红细胞Ca(2+)依赖性钾通道的影响。我们发现，ADR的蒽环部分可增加低浓度普萘洛尔诱导的红细胞Ca(2+)依赖性钾外流，而ADR全分子对普萘洛尔或A23187诱导的Ca(2+)依赖性钾通道以及Pb(2+)依赖性钾外流均无影响。溴化乙锭、维拉帕米和三氟拉嗪可抑制高剂量普萘洛尔诱导的Ca(2+)依赖性钾外流。ADR的蒽环部分能够消除溴化乙锭和维拉帕米的阻断作用，但不影响三氟拉嗪的阻断作用。我们还发现，ADR与Fe2+、Cu2+和Co2+形成的复合物是普萘洛尔诱导的Ca(2+)依赖性钾外流的有效抑制剂，但不是Pb(2+)依赖性钾外流的抑制剂。相反，ADR-Fe3+复合物可激活人红细胞的钾通透性。提示ADR的蒽环部分及其与过渡金属形成的复合物对普萘洛尔诱导的Ca(2+)依赖性钾通道产生相反作用，是由于它们对Ca2+进入细胞的途径有影响，而非直接作用于钾通道。
