Abstract | BACKGROUND & AIMS: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder. METHODS: RESULTS:
Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration. CONCLUSIONS: Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.
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Authors | Hasan Kulaksiz, Thorsten Schlenker, Daniel Rost, Adolf Stiehl, Martin Volkmann, Thomas Lehnert, Yalcin Cetin, Wolfgang Stremmel |
Journal | Gastroenterology
(Gastroenterology)
Vol. 126
Issue 3
Pg. 732-40
(Mar 2004)
ISSN: 0016-5085 [Print] United States |
PMID | 14988827
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CFTR protein, human
- Chlorides
- Gastrointestinal Hormones
- Natriuretic Peptides
- Peptides
- Proteins
- Cystic Fibrosis Transmembrane Conductance Regulator
- guanylin
- Cyclic AMP
- Cyclic GMP-Dependent Protein Kinases
- Guanylate Cyclase
- Cyclic GMP
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Topics |
- Bile
(physiology)
- Cell Line
- Chlorides
(metabolism)
- Cyclic AMP
(metabolism)
- Cyclic GMP
(metabolism)
- Cyclic GMP-Dependent Protein Kinases
(metabolism)
- Cystic Fibrosis Transmembrane Conductance Regulator
(metabolism)
- Gallbladder
(metabolism)
- Gastrointestinal Hormones
(physiology)
- Guanylate Cyclase
(metabolism)
- Humans
- Natriuretic Peptides
- Peptides
(physiology)
- Proteins
(metabolism)
- Signal Transduction
(physiology)
- Tissue Distribution
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