期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 107, 期 12, 页码 1563-1569出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI11234
关键词
-
资金
- NIDDK NIH HHS [R01 DK048482, P01 DK020543, DK48482, R37 DK039298, DK39228, R29 DK048482, DK20543, R01 DK039298] Funding Source: Medline
Decreases in blood pH activate NHE3, the proximal tubular apical membrane Na/H antiporter. In cultured renal epithelial cells, activation of the endothelin-B (ETB) receptor increases NHE3 activity. To examine the role of the ETB receptor in the response to acidosis in vivo, the present studies examined ETB receptor-deficient mice, rescued from neonatal lethality by expression of a dopamine beta -hydroxylase promoter/ETB receptor transgene (Tg/Tg:ETB-/- mice). In proximal tubule suspensions from Tg/Tg:ETB+/- mice, 10(-8) M endothelin-l (ET-1) increased NHE3 activity, but this treatment had no effect on tubules from Tg/Tg:ETB-/- mice. Acid ingestion for 7 days caused a greater decrease in blood HCO3- concentration in Tg/Tg:ETB-/- mice compared with Tg/Tg:ETB+/+ and Tg/Tg:ETB+/- mice. Whereas acid ingestion increased apical membrane NHE3 by 42-46% in Tg/Tg:ETB+/+ and Tg/Tg:ETB+/- mice, it had no effect on NHE3 in Tg/Tg:ETB-/- mice. In C57BL/6 mice, excess acid ingestion increased renal cortical preproET-1 mRNA expression 2.4-fold and decreased preproET-3 mRNA expression by 37%. On a control diet, Tg/Tg ETB-/- mice had low rates of ammonium excretion, which could not be attributed to an inability to acidify the urine, as well as hypercitraturia, with increased titratable acid excretion. Acid ingestion increased ammonium excretion, citrate absorption, and titratable acid excretion to the same levels in Tg/Tg:ETB-/- and Tg/Tg:ETB+/+ mice. In conclusion, metabolic acidosis increases ET-1 expression, which increases NHE3 activity via the ETB receptor.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据