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Research Article Free access | 10.1172/JCI2821

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

L Fouassier, T Chinet, B Robert, A Carayon, P Balladur, M Mergey, A Paul, R Poupon, J Capeau, V Barbu, and C Housset

Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Unité Institut National de la Santé et de la Recherche Médicale U402, Faculté de Médecine Saint-Antoine, 75012 Paris, France.

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Published June 15, 1998 - More info

Published in Volume 101, Issue 12 on June 15, 1998
J Clin Invest. 1998;101(12):2881–2888. https://doi.org/10.1172/JCI2821.
© 1998 The American Society for Clinical Investigation
Published June 15, 1998 - Version history
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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 receptor, cAMP-dependent anion secretion in human gallbladder epithelium, indicating a role in the control of bile secretion by an autocrine/paracrine mechanism.

Version history
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