Polarized expression and function of P2Y ATP receptors in rat bile duct epithelia

Jonathan A. Dranoff, Anatoly I. Masyuk, Emma A. Kruglov, Nicholas F La Russo, Michael H. Nathanson

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Extracellular nucleotides may be important regulators of bile ductular secretion, because cholangiocytes express P2Y ATP receptors and nucleotides are found in bile. However, the expression, distribution, and function of specific P2Y receptor subtypes in cholangiocytes are unknown. Thus our aim was to determine the subtypes, distribution, and role in secretion of P2Y receptors expressed by cholangiocytes. The molecular subtypes of P2Y receptors were determined by RT-PCR. Functional studies measuring cytosolic Ca2+ (Cai 2+) signals and bile ductular pH were performed in isolated, microperfused intrahepatic bile duct units (IBDUs). PCR products corresponding to P2Y1, P2Y2, P2Y4, P2Y6, and P2X4 receptor subtypes were identified. Luminal perfusion of ATP into IBDUs induced increases in Ca2+ that were inhibited by apyrase and suramin. Luminal ATP, ADP, 2-methylthio-adenosine 5′-triphosphate, UTP, and UDP each increased Cai 2+. Basolateral addition of adenosine 5′-O-(3-thiotriphosphate) (ATP-γ-S), but not ATP, to the perifusing bath increased Cai 2+. IBDU perfusion with ATP-γ-S induced net bile ductular alkalization. Cholangiocytes express multiple P2Y receptor subtypes that are expressed at the apical plasma membrane domain. P2Y receptors are also expressed on the basolateral domain, but their activation is attenuated by nucleotide hydrolysis. Activation of ductular P2Y receptors induces net ductular alkalization, suggesting that nucleotide signaling may be an important regulator of bile secretion by the liver.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number4 44-4
StatePublished - 2001

Fingerprint

Purinergic P2 Receptors
Bile Ducts
Bile
Intrahepatic Bile Ducts
Epithelium
Adenosine Triphosphate
Nucleotides
Purinergic P2X4 Receptors
Perfusion
Purinergic P2Y2 Receptors
Purinergic P2Y1 Receptors
Apyrase
Suramin
Polymerase Chain Reaction
Uridine Triphosphate
Uridine Diphosphate
Baths
Adenosine Diphosphate
Hydrolysis
Cell Membrane

Keywords

  • Calcium
  • Chloride
  • Nucleoside triphosphate diphosphohydrolase
  • Nucleotide
  • Purinoceptor
  • Secretion

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Polarized expression and function of P2Y ATP receptors in rat bile duct epithelia. / Dranoff, Jonathan A.; Masyuk, Anatoly I.; Kruglov, Emma A.; La Russo, Nicholas F; Nathanson, Michael H.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 4 44-4, 2001.

Research output: Contribution to journalArticle

Dranoff, Jonathan A. ; Masyuk, Anatoly I. ; Kruglov, Emma A. ; La Russo, Nicholas F ; Nathanson, Michael H. / Polarized expression and function of P2Y ATP receptors in rat bile duct epithelia. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2001 ; Vol. 281, No. 4 44-4.
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