MUSCARINIC ACETYLCHOLINE-RECEPTOR STIMULATION OF BILIARY EPITHELIAL-CELLS AND ITS EFFECT ON BILE SECRETION IN THE ISOLATED-PERFUSED RAT-LIVER

The aim was to explore whether biliary epithelial cells show muscarini c acetylcholine receptors and to investigate their role in ductular bi le formation. In both, isolated rat biliary epithelial cells and Mz-Ch a-1 cells, a biliary epithelial cell line, binding of [H-3]N-methyl-sc opolamine occurred with 0.718 +/- 0.08 and 0.482 +/- 0.05 fmol per 10( 6) cells, respectively, To characterize the involved second messenger, intracellular Ca2+ levels were monitored by confocal microscopy, Stim ulation of biliary epithelial cells with carbachol produced an increas e in free cytosolic Ca2+ levels that declined to baseline values descr ibing a sinusoidal oscillation curve, Increasing concentrations of the agonist decreased latency of the response and increased oscillation f requency. Similar results were obtained in Mz-Cha-1 cells, The intrace llular Ca2+ originated from IP3 sensitive intracellular stores and fro m the extracellular medium, The Ca2+ response could partially be block ed by atropine and completely by pirenzepine, a specific muscarinic re ceptor-type M1 antagonist, The presence of M1 receptor messenger RNA ( mRNA) in biliary epithelial cells was confirmed by reverse transcripta se polymerase chain reaction. In the isolated perfused guinea pig live r, a model with high ductular bile now, carbachol induced a dose depen dent decrease of bile flow by 79.6% +/- 9.8% at 50 mu mol/L carbachol (P < .001), without affecting perfusion pressure or biliary electrolyt e concentrations, It is concluded that biliary epithelial cells expres s muscarinic acetylcholine receptors, Stimulation of this receptor lea ds to cholestasis, This could be because of changes in peribiliary per meability and/or inhibition of biliary epithelial cell secretory funct ion.