ENDOTHELIN-1 SECRETION BY HUMAN GALLBLADDER EPITHELIAL-CELLS IN PRIMARY CULTURE

BACKGROUND: The three isoforms of endothelin (ET), ET-1, ET-2, and ET-3 are potent contractile agonists for smooth muscle in a wide variety of tissues including the gallbladder. There is increasing evidence that endothelin acts in a paracrine fashion, however its cell source in the gallbladder is unclear. EXPERIMENTAL DESIGN: To examine the production of ET by gallbladder and bile duct epithelium. RESULTS: We show that human gallbladder epithelial cells in primary culture secrete endothelin. ET release was time-dependent, and intracellular ET was negligible, indicating de novo synthesis. Secretion was increased by physiologic concentrations of cholecystokinin. Epithelial cells lining hepatic cysts in primary culture also released ET, suggesting that the intrahepatic, as well as the extrahepatic biliary epithelium is a source of this cytokine. High performance liquid chromatography separation of the conditioned medium from both cell types showed a single peak corresponding to that of ET-1. In vivo, ET-1 was present in hepatic cyst fluid, but was not detectable in gallbladder or choledochal bile. On tissue sections, both intrahepatic and extrahepatic bile duct epithelial cells were labeled with an anti-''big'' ET-1 polyclonal antibody. CONCLUSIONS: These results suggest that ET-1 is locally produced in the biliary tract and by a paracrine route, could play a role in choledochal motility and gallbladder contraction.