Stimulation of ATP secretion in the liver by therapeutic bile acids

M. H. Nathanson, A. D. Burgstahler, A. Masyuk, Nicholas F La Russo

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

ATP receptors are ubiquitously expressed and are potential targets for the therapy of a number of disorders. However, delivery of ATP or other nucleotides to specific tissues is problematic, and no pharmacological means to stimulate the release of endogenous ATP has been described. We examined the effects of the bile acid ursodeoxycholic acid (UDCA) on ATP release into bile, since this bile acid is the only agent known to be of therapeutic benefit in secretory disorders of the liver, and since its mechanism of action is not established. Both UDCA and its taurine conjugate stimulated secretion of ATP by isolated rat hepatocytes, and produced measurable increases in ATP in bile of isolated rat liver. Perfusion of ATP into microdissected bile-duct segments induced Ca2+ signalling in bile-duct epithelia, while perfusion of bile acid did not. Thus UDCA may promote bile flow by inducing hepatocytes to release ATP into bile, which then stimulates fluid and electrolyte secretion by bile-duct epithelia downstream via changes in cytosolic Ca2+. Moreover, these findings demonstrate the feasibility of using pharmacological means to induce secretion of endogenous ATP. Since the liver and other epithelial organs express luminal ATP receptors, these findings more generally suggest that a mechanism exists for pharmacological activation of this paracrine signalling pathway. This strategy may be useful for treatment of cystic fibrosis and other secretory disorders of the liver and other epithelial tissues.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalBiochemical Journal
Volume358
Issue number1
DOIs
StatePublished - Aug 15 2001
Externally publishedYes

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Bile Acids and Salts
Liver
Adenosine Triphosphate
Bile
Ursodeoxycholic Acid
Bile Ducts
Ducts
Purinergic P2 Receptors
Epithelium
Pharmacology
Therapeutics
Rats
Hepatocytes
Perfusion
Paracrine Communication
Tissue
Fluids and Secretions
Taurine
Cystic Fibrosis
Electrolytes

Keywords

  • Bile duct
  • Cholestasis
  • Cystic fibrosis
  • P2Y receptor
  • Ursodeoxycholic acid

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stimulation of ATP secretion in the liver by therapeutic bile acids. / Nathanson, M. H.; Burgstahler, A. D.; Masyuk, A.; La Russo, Nicholas F.

In: Biochemical Journal, Vol. 358, No. 1, 15.08.2001, p. 1-5.

Research output: Contribution to journalArticle

Nathanson, M. H. ; Burgstahler, A. D. ; Masyuk, A. ; La Russo, Nicholas F. / Stimulation of ATP secretion in the liver by therapeutic bile acids. In: Biochemical Journal. 2001 ; Vol. 358, No. 1. pp. 1-5.
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