通过自分泌机制刺激OKP细胞中的NHE3

Stimulation of NHE3 in OKP cells by an autocrine mechanism.

作者信息

Amemiya Morimasa, Mori Honami, Imamura Shigeki, Toyoda Akira, Funayama Izumi, Asano Yasushi, Kusano Eiji, Tabei Kaoru

机构信息

Department of Internal Medicine, Division of Nephrology, Jichi Omiya Medical Center, Jichi Medical School, Saitama-shi, Saitama-Ken, Japan.

出版信息

Nephron Exp Nephrol. 2004;96(1):e23-30. doi: 10.1159/000075573.

DOI:10.1159/000075573

PMID:14752245

Abstract

BACKGROUND/AIMS: Chronic hypokalemia increases NHE3 activity in OKP cells. The aim of the present study was to determine whether an autocrine mechanism is involved in this activation.

METHODS

After incubation of OKP cells in normal-K(+) and low-K(+) media for 24 h, the potassium concentration in the low-K(+) media was adjusted to a normal level. These conditioned media were then used as the normal-K(+) and low-K(+) supernatants. Other OKP cells were incubated in these normal-K(+) and low-K(+) supernatants and the mechanism of Na(+)/H(+) antiporter activation was examined.

RESULTS

The EIPA-resistant Na(+)/H(+) antiporter activity of OKP cells increased after 4 h incubation in the low-K(+) supernatant, and the amount of NHE3 protein increased at 24 h. Since both BQ788 and saralasin blocked this antiporter activation, the supernatant concentration of endothelin I (ET-I) and angiotensin II (Ang-II) were measured. The ET-I concentration was reduced, but the Ang-II concentration remained unchanged. There was a significant association between a reduction in the ET-I concentration and an increase in Na(+)/H(+) antiporter activity, but only when Ang-II was present in the supernatant.

CONCLUSION

An autocrine mechanism is involved in the activation of NHE3 in OKP cells. Both ET-I and Ang-II play a role in this activation.

摘要

背景/目的：慢性低钾血症会增加OKP细胞中NHE3的活性。本研究的目的是确定自分泌机制是否参与这种激活过程。

方法

将OKP细胞在正常钾（K⁺）和低钾培养基中孵育24小时后，将低钾培养基中的钾浓度调整至正常水平。然后将这些条件培养基用作正常钾和低钾上清液。将其他OKP细胞在这些正常钾和低钾上清液中孵育，并检测钠/氢（Na⁺/H⁺）反向转运体激活的机制。

结果

在低钾上清液中孵育4小时后，OKP细胞的EIPA抗性Na⁺/H⁺反向转运体活性增加，NHE3蛋白量在24小时时增加。由于BQ788和沙拉新均阻断了这种反向转运体的激活，因此检测了内皮素I（ET-I）和血管紧张素II（Ang-II）的上清液浓度。ET-I浓度降低，但Ang-II浓度保持不变。ET-I浓度降低与Na⁺/H⁺反向转运体活性增加之间存在显著关联，但仅当Ang-II存在于上清液中时才如此。