Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate- dependent anion secretion by an autocrine/paracrine mechanism in gallbladder epithelial cells

The Journal of Clinical Investigation
L FouassierC Housset

Abstract

Ion and fluid transport across the biliary epithelium contributes to bile secretion. Since endothelin (ET)-1 affects ion transport activities and is released by human gallbladder- derived biliary epithelial cells in primary culture, we examined the expression of ET peptides and ET receptors and the influence of ET-1 on ion transport in this epithelium ex vivo. In freshly isolated gallbladder epithelial cells, preproET-1, -2, and -3 mRNAs were detected by reverse transcription PCR and ET-1 isopeptide was identified by chromatography. The cells also displayed ET receptor mRNAs and high-affinity binding sites for ET-1, mostly of the ETB type. Electrogenic anion secretion across intact gallbladder mucosa was stimulated by forskolin, secretin, and exogenous ATP, as assessed by short-circuit current (Isc) increases in Ussing-type chambers. ET-1 inhibited forskolin- and secretin-induced changes in Isc, without affecting baseline Isc or ATP-induced changes. Accordingly, ET-1 significantly reduced the accumulation of intracellular cAMP elicited by forskolin and secretin in the epithelial cells, and this effect was abolished by pertussis toxin. This is the first evidence that ET-1 is synthesized and inhibits, via a Gi protein-coupled rec...Continue Reading

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Citations

May 2, 2002·Journal of Gastroenterology and Hepatology·Bilal O Al-JiffryGino T P Saccone
Oct 7, 2006·Current Opinion in Gastroenterology·R T Prall, N F Larusso
Mar 11, 2005·Journal of Clinical Gastroenterology·Michael B Fallon
Mar 11, 2003·American Journal of Respiratory Cell and Molecular Biology·Sabine BlouquitThierry Chinet
Mar 18, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Giammarco FavaGianfranco Alpini
Apr 18, 2000·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·T UchideK Saida
Aug 25, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Rahul KuverSum P Lee
Oct 13, 2006·Current Opinion in Gastroenterology·R T Prall, N F Larusso
Jun 11, 1999·The American Journal of Physiology·R M RomanJ G Fitz
Oct 29, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·P J Gunter-SmithR Terrell
May 1, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gianfranco AlpiniNicholas F Larusso
Nov 8, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Nicolas ChignardChantal Housset
Aug 24, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·N KannoG Alpini
Jul 9, 2003·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·J W C ChenG T P Saccone
Jul 7, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Laura FouassierChantal Housset

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