Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells

C. Sauvant, D. Hesse, H. Holzinger, K. K. Evans, William H Dantzler, M. Gekle

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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. PGE2 binds 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 true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) 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. PGE 2 stimulated 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 that 1) stimulation of basolateral organic anion uptake by EGF or PGE2 is 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 PGE2 is 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 PGE2 in opossum kidney cells and rabbit S2 segments, and 5) stimulation of basolateral OAT1 by EGF or PGE2 is also important in humans and, thus, may have clinical implications.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number4 55-4
StatePublished - Apr 2004

Fingerprint

Proximal Kidney Tubule
Dinoprostone
Anions
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Rabbits
Kidney
Opossums
Prostaglandins
Cell Line
Phospholipases A2
Prostaglandins E
Adenylyl Cyclases
Arachidonic Acid
Artifacts
Signal Transduction
Cell Culture Techniques

Keywords

  • Basolateral transport
  • Epithelial growth factor
  • Extracellular signal-regulated kinase 1/2
  • IHKE cells
  • Mitogen-activated protein kinase
  • Mitogen-activated protein kinase kinase
  • Organic anion transport
  • Rabbit isolated proximal tubule

ASJC Scopus subject areas

  • Physiology

Cite this

Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells. / Sauvant, C.; Hesse, D.; Holzinger, H.; Evans, K. K.; Dantzler, William H; Gekle, M.

In: American Journal of Physiology - Renal Physiology, Vol. 286, No. 4 55-4, 04.2004.

Research output: Contribution to journalArticle

@article{50774efb980b43c2bcbe9d84bc5f3f45,
title = "Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells",
abstract = "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. PGE2 binds 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 true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) 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. PGE 2 stimulated 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 that 1) stimulation of basolateral organic anion uptake by EGF or PGE2 is 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 PGE2 is 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 PGE2 in opossum kidney cells and rabbit S2 segments, and 5) stimulation of basolateral OAT1 by EGF or PGE2 is also important in humans and, thus, may have clinical implications.",
keywords = "Basolateral transport, Epithelial growth factor, Extracellular signal-regulated kinase 1/2, IHKE cells, Mitogen-activated protein kinase, Mitogen-activated protein kinase kinase, Organic anion transport, Rabbit isolated proximal tubule",
author = "C. Sauvant and D. Hesse and H. Holzinger and Evans, {K. K.} and Dantzler, {William H} and M. Gekle",
year = "2004",
month = "4",
language = "English (US)",
volume = "286",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "4 55-4",

}

TY - JOUR

T1 - Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells

AU - Sauvant, C.

AU - Hesse, D.

AU - Holzinger, H.

AU - Evans, K. K.

AU - Dantzler, William H

AU - Gekle, M.

PY - 2004/4

Y1 - 2004/4

N2 - 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. PGE2 binds 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 true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) 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. PGE 2 stimulated 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 that 1) stimulation of basolateral organic anion uptake by EGF or PGE2 is 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 PGE2 is 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 PGE2 in opossum kidney cells and rabbit S2 segments, and 5) stimulation of basolateral OAT1 by EGF or PGE2 is also important in humans and, thus, may have clinical implications.

AB - 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. PGE2 binds 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 true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) 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. PGE 2 stimulated 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 that 1) stimulation of basolateral organic anion uptake by EGF or PGE2 is 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 PGE2 is 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 PGE2 in opossum kidney cells and rabbit S2 segments, and 5) stimulation of basolateral OAT1 by EGF or PGE2 is also important in humans and, thus, may have clinical implications.

KW - Basolateral transport

KW - Epithelial growth factor

KW - Extracellular signal-regulated kinase 1/2

KW - IHKE cells

KW - Mitogen-activated protein kinase

KW - Mitogen-activated protein kinase kinase

KW - Organic anion transport

KW - Rabbit isolated proximal tubule

UR - http://www.scopus.com/inward/record.url?scp=1642376462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642376462&partnerID=8YFLogxK

M3 - Article

C2 - 14644751

AN - SCOPUS:1642376462

VL - 286

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 4 55-4

ER -