Function of gall bladder cholinergic brush cells

• Applicants: Professor Dr. Wolfgang Kummer; Professor Dr. Burkhard Schütz
• Subject Area: Gastroenterology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316451980

The gall bladder and bile ducts harbor brush cells in their epithelia; cells which are characterized by a brush of stiff microvilli on their apical surface. Recently, we described that mouse gastro-intestinal and hepatic-biliary brush cells have a cholinergic phenotype and that they express components of the canonical taste transduction cascade. We postulate that these brush cells are chemosensors and act as sentinels that detect harmful substances, e.g. gut bacteria, at the entrance into the hepatic-biliary system, and prevent their ascension. Using normal and transgenic mice as model organisms we intend to uncover if gall bladder cholinergic brush cells detect bacterial fermentation products or growth-promoting substrates via the canonical signal transduction cascade; if subsequently a protective acetylcholine-mediated direct or indirect contraction of the gall bladder is initiated with the purpose to flush the gall bladder; and if a (neurogenic) inflammation is initiated through local release of acetylcholine. With our project we pursue the overall goal to better understand a potential key passage in the pathogenesis of frequent and serious diseases of the hepatic-biliary system, and ultimately to be able to deduce new diagnostic and therapeutic options.

• DFG Programme: Research Grants