Tokushige A, Higashino H, Searle B M, Tamura H, Kino M, Bogden J D, Aviv A
Hypertension. 1984 Jan-Feb;6(1):20-6. doi: 10.1161/01.hyp.6.1.20.
The present study focuses on the interaction between cadmium (Cd) and the Na, K-ATPase system in in vitro grown vascular smooth muscle cells (VSMCs) derived from the rat carotid artery. In disrupted VSMCs rendered permeable by osmotic shock, Cd inhibited Na, K-ATPase; I50 was reached at 10(-5) M Cd. Mg-ATPase was also inhibited by Cd; I50 was attained at concentrations of 10(-4) M Cd. Cd inhibition of Na,K-ATPase in the VSMCs was noncompetitive with respect to Na, K, and ATP. Rubidium transport experiments performed with intact VSMCs demonstrated that within an incubation period of 150 minutes, a concentration of 10(-4) M Cd in the extracellular fluid exerted no acute effect on the Na-K pump. Within this time interval, intracellular Cd attained a concentration eightfold higher than the extracellular Cd concentration. Thus, it appears that under acute conditions Cd exerts its inhibitory effect on Na, K-ATPase only in disrupted VSMCs. The data further suggest that, in the VSMC, conditions under which Cd inhibits Na, K-ATPase are consistent with inhibition from the cytoplasmic side of the cell membrane.
本研究聚焦于镉(Cd)与体外培养的源自大鼠颈动脉的血管平滑肌细胞(VSMC)中钠钾ATP酶系统之间的相互作用。在经渗透压休克处理而变得通透的破碎VSMC中,Cd抑制钠钾ATP酶;在Cd浓度为10⁻⁵ M时达到半数抑制浓度(I50)。镁ATP酶也受到Cd抑制;在Cd浓度为10⁻⁴ M时达到I50。VSMC中Cd对钠钾ATP酶的抑制作用在钠、钾和ATP方面是非竞争性的。用完整VSMC进行的铷转运实验表明,在150分钟的孵育期内,细胞外液中10⁻⁴ M的Cd浓度对钠钾泵没有急性影响。在此时间间隔内,细胞内Cd的浓度达到细胞外Cd浓度的八倍。因此,在急性条件下,Cd似乎仅在破碎的VSMC中对钠钾ATP酶发挥抑制作用。数据进一步表明,在VSMC中,Cd抑制钠钾ATP酶的条件与从细胞膜细胞质侧的抑制作用一致。