Haber R S, Ismail-Beigi F, Loeb J N
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Endocrinology. 1988 Jul;123(1):238-47. doi: 10.1210/endo-123-1-238.
To elucidate the relationship between the stimulation of Na+ and K+ fluxes by thyroid hormone and the induction of the Na,K-ATPase, we performed a detailed comparison of the time courses of these hormonal effects in a rat liver cell line, clone 9. Stimulations of passive K+ efflux, passive Na+ influx, and ouabain-inhibitable K+ uptake were all evident within 6-12 h of exposure of cells to T3 (10(-7) M). The time course of the induction of Na,K-ATPase activity closely paralleled that of the increase in the rate of Na+ and K+ fluxes. The maximal stimulatory effects of T3 on ouabain-inhibitable K+ uptake and Na,K-ATPase activity at 72 h were +49% and +36%, respectively. Intracellular Na+ and K+ contents were virtually unchanged during these increases in ion fluxes and Na,K-ATPase activity, suggesting an efficient homeostatic adaptation to the augmented passive "leak" of Na+ and K+ down their transmembrane concentration gradients. T3 treatment for 72 h was also shown to stimulate both lactate production (+62%) and [3H]2-deoxyglucose uptake (+82%) in these cells. The onset of these effects appeared to precede that of the stimulation of Na+ and K+ fluxes, being detectable at 4 h. Neither these latter effects of T3 nor the stimulation of ouabain-inhibitable K+ uptake could be demonstrated when RNA or protein synthesis was inhibited by actinomycin D or cycloheximide, respectively. It is concluded that in clone 9 cells thyroid hormone causes increases in passive Na+ influx, passive K+ efflux, active Na,K transport, and Na,K-ATPase activity whose time courses are closely parallel.
为阐明甲状腺激素对钠钾离子通量的刺激作用与钠钾 -ATP 酶诱导之间的关系，我们在大鼠肝细胞系克隆 9 中对这些激素效应的时间进程进行了详细比较。在细胞暴露于 T3（10⁻⁷ M）后的 6 - 12 小时内，被动钾离子外流、被动钠离子内流以及哇巴因抑制的钾离子摄取均明显增加。钠钾 -ATP 酶活性诱导的时间进程与钠钾离子通量增加的时间进程密切平行。在 72 小时时，T3 对哇巴因抑制的钾离子摄取和钠钾 -ATP 酶活性的最大刺激作用分别为 +49% 和 +36%。在离子通量和钠钾 -ATP 酶活性增加的过程中，细胞内钠钾离子含量几乎没有变化，这表明细胞对钠离子和钾离子沿其跨膜浓度梯度增加的被动“渗漏”进行了有效的稳态适应。还发现 T3 处理 72 小时可刺激这些细胞中的乳酸生成（+62%）和 [³H]2 - 脱氧葡萄糖摄取（+82%）。这些效应的起始似乎先于钠钾离子通量的刺激，在 4 小时时即可检测到。当分别用放线菌素 D 或环己酰亚胺抑制 RNA 或蛋白质合成时，T3 的这些后期效应以及哇巴因抑制的钾离子摄取的刺激作用均无法得到证实。结论是，在克隆 9 细胞中，甲状腺激素导致被动钠离子内流、被动钾离子外流、主动钠钾转运以及钠钾 -ATP 酶活性增加，其时间进程密切平行。
