Mechanisms of inactivation of the action of aldosterone on collecting duct by TGF-β

被引:27
作者
Husted, RF
Sigmund, RD
Stokes, JB
机构
[1] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[2] Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA
关键词
sodium transport; inner medullary collecting duct; epithelial sodium channel; sodium-potassium-adenosinetriphosphatase; benzamil; glucocorticoid; mineralocorticoid; Northern blot; ribonuclease protection assay; electrophysiology;
D O I
10.1152/ajprenal.2000.278.3.F425
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The purpose of these experiments was to investigate the mechanisms whereby transforming growth factor-beta (TGF-beta) antagonizes the action of adrenocorticoid hormones on Na(+) transport by the rat inner medullary collecting duct in primary culture. Steroid hormones 1) increased Na(+) transport by three- to fourfold, 2) increased the maximum capacity of the Na(+)-K(+) pump by 30-50%, 3) increased the steady-state levels of the alpha(1)-subunit of the Na(+)-K(+)-ATPase by similar to 30%, and 4) increased the steady-state levels of the alpha-subunit of the rat epithelial Na(+) channel (alpha-rENaC) by nearly fourfold. TGF-beta blocked the effects of steroids on the increase in Na(+) transport and the stimulation of the Na(+)-K(+)-ATPase and pump capacity. However, there was no effect of TGF-beta on the steroid-induced increase in mRNA levels of alpha-rENaC. The effects of TGF-beta were not secondary to the decrease in Na(+) transport per se, inasmuch as benzamil inhibited the increase in Na(+) transport but did not block the increase in pump capacity or Na(+)-K(+)-ATPase mRNA. The results indicate that TGF-beta does not inactivate the steroid receptor or its translocation to the nucleus. Rather, they indicate complex pathways involving interruption of the enhancement of pump activity and activation/inactivation of pathways distal to the steroid-induced increase in the transcription of alpha-rENaC.
引用
收藏
页码:F425 / F433
页数:9
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