Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells.
Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells.
复制标题
EGF和PGE2对兔近端肾小管基底外侧有机阴离子摄取和人肾上皮细胞表达的hOAT1的作用。
DOI：
10.1152/ajprenal.00326.2003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Gekle,M
中科院分区：
文献类型：
--
作者：
Sauvant,C;Hesse,D;Holzinger,H;Evans,KK;Dantzler,WH;Gekle,M
We recently showed that, in a proximal tubule cell line (opossum kidney cells), epithelial growth factor (EGF) stimulates basolateral organic anion transport (OAT) via ERK1/2, arachidonic acid, phospholipase A2, and generation of prostaglandins. PGE2binds the prostanoid receptor and, thus, activates adenylate cyclase and PKA, which stimulate basolateral organic anion uptake. In the present study, we investigated whether this regulatory cascade is also true1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and2) in a human renal epithelial cell line stably expressing human OAT1 (IHKE-hOAT1). EGF activated ERK1/2 in S2 tubules and IHKE-hOAT1, and, in both cases, inhibition of ERK activation (by U-0126) abolished this stimulation. In S2 tubules and IHKE-hOAT1, EGF led to an increase of organic anion uptake, which again was inhibited by U-0126. PGE2stimulated basolateral organic anion uptake in rabbit S2 tubules and IHKE-hOAT1. EGF- and PGE2-mediated stimulation of organic anion uptake was abolished by inhibition of PKA in rabbit S2 tubules and IHKE-hOAT1, respectively. We conclude that1) stimulation of basolateral organic anion uptake by EGF or PGE2is a widespread (if not general) regulatory mechanism,2) the signal transduction pathway involved seems to be general,3) stimulation of basolateral organic anion uptake by EGF or PGE2is also present under ex vivo conditions and, thus, is not a cell culture artifact,4) activation of OAT1 is sufficient to explain the stimulatory effects of EGF and PGE2in opossum kidney cells and rabbit S2 segments, and5) stimulation of basolateral OAT1 by EGF or PGE2is also important in humans and, thus, may have clinical implications.
