Identification of lactate as a driving force for prostanoid transport by prostaglandin transporter PGT

Brenda S. Chan, Shinichi Endo, Naoaki Kanai, Victor L. Schuster

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

We previously characterized the prostaglandin (PG) transporter PGT as an exchanger in which [3H]PGE2 influx is coupled to the efflux of a countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT under conditions known to favor glycolysis (glucose as a carbon source) or oxidative phosphorylation (glutamine as a carbon source) and studied the effect on PGT-mediated [3H]PGE2 influx. PGT-expressing cells grown in glutamine exhibited a 2- to 4-fold increase in [3H]PGE2 influx compared with the antisense control, whereas cells grown in glucose exhibited a 14-fold increase. In the presence of 10 vs. 25 mM glucose during the uptake, there was a dose-dependent increment in [3H]PGE2 influx. Cis inhibition of [3H]PGE2 influx occurred with lactate at physiological concentrations (apparent Km = 48 ± 12 mM). Preloading with lactate caused a dose-dependent trans stimulation of PGT-mediated [3H]PGE2 uptake, and external lactate caused trans stimulation of PGT-mediated [3H]PGE2 release. Together, these data are consistent with PGT-mediated PG-lactate exchange. Cells engaged in glycolysis would then be poised energetically for prostanoid uptake by means of PGT.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number6 51-6
StatePublished - 2002

Fingerprint

Dinoprostone
Prostaglandins
Lactic Acid
Glycolysis
Glutamine
Glucose
Carbon
Oxidative Phosphorylation
HeLa Cells
Cultured Cells

Keywords

  • Biological transport
  • Glycolysis
  • Organic anion transport

ASJC Scopus subject areas

  • Physiology

Cite this

Identification of lactate as a driving force for prostanoid transport by prostaglandin transporter PGT. / Chan, Brenda S.; Endo, Shinichi; Kanai, Naoaki; Schuster, Victor L.

In: American Journal of Physiology - Renal Physiology, Vol. 282, No. 6 51-6, 2002.

Research output: Contribution to journalArticle

@article{0e0f3cf4961a499a969b13deef68e252,
title = "Identification of lactate as a driving force for prostanoid transport by prostaglandin transporter PGT",
abstract = "We previously characterized the prostaglandin (PG) transporter PGT as an exchanger in which [3H]PGE2 influx is coupled to the efflux of a countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT under conditions known to favor glycolysis (glucose as a carbon source) or oxidative phosphorylation (glutamine as a carbon source) and studied the effect on PGT-mediated [3H]PGE2 influx. PGT-expressing cells grown in glutamine exhibited a 2- to 4-fold increase in [3H]PGE2 influx compared with the antisense control, whereas cells grown in glucose exhibited a 14-fold increase. In the presence of 10 vs. 25 mM glucose during the uptake, there was a dose-dependent increment in [3H]PGE2 influx. Cis inhibition of [3H]PGE2 influx occurred with lactate at physiological concentrations (apparent Km = 48 ± 12 mM). Preloading with lactate caused a dose-dependent trans stimulation of PGT-mediated [3H]PGE2 uptake, and external lactate caused trans stimulation of PGT-mediated [3H]PGE2 release. Together, these data are consistent with PGT-mediated PG-lactate exchange. Cells engaged in glycolysis would then be poised energetically for prostanoid uptake by means of PGT.",
keywords = "Biological transport, Glycolysis, Organic anion transport",
author = "Chan, {Brenda S.} and Shinichi Endo and Naoaki Kanai and Schuster, {Victor L.}",
year = "2002",
language = "English (US)",
volume = "282",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6 51-6",

}

TY - JOUR

T1 - Identification of lactate as a driving force for prostanoid transport by prostaglandin transporter PGT

AU - Chan, Brenda S.

AU - Endo, Shinichi

AU - Kanai, Naoaki

AU - Schuster, Victor L.

PY - 2002

Y1 - 2002

N2 - We previously characterized the prostaglandin (PG) transporter PGT as an exchanger in which [3H]PGE2 influx is coupled to the efflux of a countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT under conditions known to favor glycolysis (glucose as a carbon source) or oxidative phosphorylation (glutamine as a carbon source) and studied the effect on PGT-mediated [3H]PGE2 influx. PGT-expressing cells grown in glutamine exhibited a 2- to 4-fold increase in [3H]PGE2 influx compared with the antisense control, whereas cells grown in glucose exhibited a 14-fold increase. In the presence of 10 vs. 25 mM glucose during the uptake, there was a dose-dependent increment in [3H]PGE2 influx. Cis inhibition of [3H]PGE2 influx occurred with lactate at physiological concentrations (apparent Km = 48 ± 12 mM). Preloading with lactate caused a dose-dependent trans stimulation of PGT-mediated [3H]PGE2 uptake, and external lactate caused trans stimulation of PGT-mediated [3H]PGE2 release. Together, these data are consistent with PGT-mediated PG-lactate exchange. Cells engaged in glycolysis would then be poised energetically for prostanoid uptake by means of PGT.

AB - We previously characterized the prostaglandin (PG) transporter PGT as an exchanger in which [3H]PGE2 influx is coupled to the efflux of a countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT under conditions known to favor glycolysis (glucose as a carbon source) or oxidative phosphorylation (glutamine as a carbon source) and studied the effect on PGT-mediated [3H]PGE2 influx. PGT-expressing cells grown in glutamine exhibited a 2- to 4-fold increase in [3H]PGE2 influx compared with the antisense control, whereas cells grown in glucose exhibited a 14-fold increase. In the presence of 10 vs. 25 mM glucose during the uptake, there was a dose-dependent increment in [3H]PGE2 influx. Cis inhibition of [3H]PGE2 influx occurred with lactate at physiological concentrations (apparent Km = 48 ± 12 mM). Preloading with lactate caused a dose-dependent trans stimulation of PGT-mediated [3H]PGE2 uptake, and external lactate caused trans stimulation of PGT-mediated [3H]PGE2 release. Together, these data are consistent with PGT-mediated PG-lactate exchange. Cells engaged in glycolysis would then be poised energetically for prostanoid uptake by means of PGT.

KW - Biological transport

KW - Glycolysis

KW - Organic anion transport

UR - http://www.scopus.com/inward/record.url?scp=0036080578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036080578&partnerID=8YFLogxK

M3 - Article

C2 - 11997326

AN - SCOPUS:0036080578

VL - 282

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 6 51-6

ER -