Barlet-Bas C, Khadouri C, Marsy S, Doucet A
Laboratoire de Physiologie Cellulaire, Collège de France, Paris.
Proc Natl Acad Sci U S A. 1988 Mar;85(5):1707-11. doi: 10.1073/pnas.85.5.1707.
The aim of this study was to develop an in vitro system in which we could study the causal relationship between short-term stimulation of Na+,K+-ATPase in the collecting tubule by aldosterone on the one hand and protein synthesis and changes in intracellular Na+ concentration on the other hand. Previous in vivo studies suggested that triiodothyronine might facilitate aldosterone-induced stimulation of Na+,K+-ATPase. Results show that when segments of cortical collecting tubules microdissected from collagenase-treated kidneys of adrenalectomized rats were incubated for 3 hr in the presence of either 10(-8) M aldosterone or 10(-8) M triiodothyronine alone Na+,K+-ATPase activity was not altered, whereas the addition of both hormones markedly stimulated the activity and the number of catalytic sites of Na+,K+-ATPase. This stimulation was abolished by actinomycin D and cycloheximide, whereas it was not altered in the absence of extracellular sodium or in the presence of the luminal Na+-channel blocker amiloride. Thus, triiodothyronine facilitates the in vitro induction of Na+,K+-ATPase synthesis by aldosterone. Aldosterone action on Na+,K+-ATPase is independent of Na+ availability.
本研究的目的是建立一种体外系统,在该系统中,一方面我们可以研究醛固酮对集合管中Na⁺,K⁺-ATP酶的短期刺激与另一方面蛋白质合成和细胞内Na⁺浓度变化之间的因果关系。先前的体内研究表明,三碘甲状腺原氨酸可能促进醛固酮诱导的Na⁺,K⁺-ATP酶刺激。结果显示,当从经胶原酶处理的肾上腺切除大鼠肾脏中显微解剖出的皮质集合管片段在单独存在10⁻⁸M醛固酮或10⁻⁸M三碘甲状腺原氨酸的情况下孵育3小时时,Na⁺,K⁺-ATP酶活性未改变,而两种激素同时添加则显著刺激了Na⁺,K⁺-ATP酶的活性和催化位点数量。放线菌素D和环己酰亚胺可消除这种刺激,而在无细胞外钠或存在管腔Na⁺通道阻滞剂阿米洛利的情况下,这种刺激未改变。因此,三碘甲状腺原氨酸促进醛固酮在体外诱导Na⁺,K⁺-ATP酶的合成。醛固酮对Na⁺,K⁺-ATP酶的作用与Na⁺的可利用性无关。