Extracellular ATP4- modulates organic anion transport by rat hepatocytes

Celeste G. Campbell, David C. Spray, Allan W. Wolkoff

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Abstract

The hepatocyte has an organic anion transport system that recognizes compounds such as bilirubin and sulfobromophthalein. These anions circulate bound tightly to albumin from which they are extracted rapidly by hepatocytes by an electroneutral process that requires extracellular inorganic anions such as Cl- for activity. Transport activity is reduced by depletion of intracellular ATP, but whether ATP interacts directly with this transporter is not known. In this study, the influence of extracellular ATP on the hepatocyte organic anion transport mechanism has been characterized. In the presence of 2.5 mM Ca2+ and 2 mM Mg2+, initial uptake of [35S]sulfobromophthalein was reduced by 50% at 1 mM ATP. In the absence of divalent cations sensitivity to ATP was 10-fold greater. Other nucleotides including UTP, CTP, GTP, ADP, AMP, and AMP-PCP (adenosine 5′-(β,-γ-methylene)triphosphate) were inactive. Decreased transport activity was rapidly reversible, was non-competitive with respect to ATP, did not require ATP hydrolysis, and did not correlate with P2y purinergic receptor activity. Differential activity of ATP on sulfobromophthalein transport in the presence and absence of divalent cations was not due to ecto-ATPase activity but rather to alteration in [ATP4-]. Although an ATP4- receptor in macrophages mediates increased cellular permeability, reduced organic anion permeability is seen in hepatocytes. This effect is not seen in the hepatoma cell line HepG2. Modulation of activity of the organic anion transporter by extracellular ATP may have important pathophysiological consequences in conditions resulting in liver cell injury.

Original languageEnglish (US)
Pages (from-to)15399-15404
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number21
StatePublished - Jul 25 1993

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Anions
Rats
Hepatocytes
Adenosine Triphosphate
Sulfobromophthalein
Divalent Cations
Permeability
Organic Anion Transporters
Purinergic Receptors
Cytidine Triphosphate
Uridine Triphosphate
Macrophages
Adenosine Monophosphate
Guanosine Triphosphate
Bilirubin
Liver
Adenosine
Adenosine Diphosphate
Albumins
Hepatocellular Carcinoma

ASJC Scopus subject areas

  • Biochemistry

Cite this

Extracellular ATP4- modulates organic anion transport by rat hepatocytes. / Campbell, Celeste G.; Spray, David C.; Wolkoff, Allan W.

In: Journal of Biological Chemistry, Vol. 268, No. 21, 25.07.1993, p. 15399-15404.

Research output: Contribution to journalArticle

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