Hyposmolality stimulates Na+/H+ exchange and HCO-3 absorption in thick ascending limb via PI 3-kinase

被引:45
作者
Good, DW
Di Mari, JF
Watts, BA
机构
[1] Univ Texas, Med Branch, Dept Med, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2000年 / 279卷 / 05期
关键词
signal transduction; adenosine 3 ' 5 '-cyclic monophosphate; phosphatidylinositol; 3-kinase; hyperosmolality;
D O I
10.1152/ajpcell.2000.279.5.C1443
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The signal transduction mechanisms that mediate osmotic regulation of Na+/H+ exchange are not understood. Recently we demonstrated that hyposmolality increases HCO3- absorption in the renal medullary thick ascending limb (MTAL) through stimulation of the apical membrane Na+/H+ exchanger NHE3. To investigate the mechanism of this stimulation, MTALs from rats were isolated and perfused in vitro with 25 mM HCO3--containing solutions. The phosphatidylinositol 3-kinase (PI 3-K) inhibitors wortmannin (100 nM) and LY-294002 (20 mM) blocked completely the stimulation of HCO3- absorption by hyposmolality. In tissue strips dissected from the inner stripe of the outer medulla, the region of the kidney highly enriched in MTALs, hyposmolality increased PI 3-K activity 2.2-fold. Wortmannin blocked the hyposmolality-induced PI 3-K activation. Further studies examined the interaction between hyposmolality and vasopressin, which inhibits HCO3- absorption in the MTAL via cAMP and often is involved in the development of plasma hyposmolality in clinical disorders. Pretreatment with arginine vasopressin, forskolin, or 8-bromo-cAMP abolished hyposmotic stimulation of HCO3- absorption, due to an effect of cAMP to inhibit hyposmolality-induced activation of PI 3-K. In contrast to their effects to block stimulation by hyposmolality, PI 3-K inhibitors and vasopressin have no effect on inhibition of apical Na+/H+ exchange (NHE3) and HCO3- absorption by hyperosmolality. These results indicate that hyposmolality increases NHE3 activity and HCO3- absorption in the MTAL through activation of a PI 3-K-dependent pathway that is inhibited by vasopressin and cAMP. Hyposmotic stimulation and hyperosmotic inhibition of NHE3 are mediated through different signal transduction mechanisms.
引用
收藏
页码:C1443 / C1454
页数:12
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