title: Deoxycholic acid induced changes in electrophysiological parameters and macromolecular permeability in murine small intestine with and without functional enteric nervous system plexuses.
abstract: BACKGROUND
  We have previously shown in mice that the fecal proportion and concentration of the hydrophobic bile acid deoxycholic acid (DCA) is elevated with high-fat feeding and that these changes are able to disrupt the intestinal barrier function. The aim of this study was to investigate whether these changes are mediated by the enteric nervous system (ENS).
  
  
  METHODS
  The function of the ENS in the small intestinal tissues of mice was compromised by two different methods: by removing the seromuscular layer and by incubating the intact tissues with tetrodotoxin (TTX), a neural conduction blocker, before DCA treatment. Tissues with or without functional plexuses were mounted into a Ussing chamber system and treated with 3 mM DCA for 20 min. After DCA treatment, the intestinal permeability to fluorescein was assessed. Short-circuit current (Isc ) and transepithelial resistance (TER) were recorded throughout the experiment.
  
  
  RESULTS
  DCA increased intestinal fluorescein permeability only in tissues where the seromuscular layer was removed. In tissues with intact seromuscular layer, DCA induced a significant increase in TER, which was attenuated by blocking of the neural function by TTX.
  
  
  CONCLUSIONS
  The results of this study suggest that the DCA-induced increase observed in fluorescein permeability is not mediated through neural pathways, but more due to a direct effect on the epithelium. However, as TTX was able to attenuate the DCA-induced increase in TER, it can be speculated that DCA is also able to elicit responses through neural pathways.
authors: Institute of Biomedicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, Helsinki, Finland.
authors: R A
authors: RA
authors: Forsgård
authors: R
authors: R
authors: Korpela
authors: L K
authors: LK
authors: Stenman
authors: P
authors: P
authors: Osterlund
authors: R
authors: R
authors: Holma
mesh_terms: D000818:Animals; D003840:Deoxycholic Acid / Q000494:pharmacology*; D055724:Electrophysiological Phenomena; D017615:Enteric Nervous System / Q000378:metabolism / Q000502:physiology*; D019793:Fluorescein / Q000737:chemistry; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability
chemical_list: D003840:Deoxycholic Acid; D019793:Fluorescein
keywords: Ussing chamber; bile acids; enteric nervous system; intestinal barrier function; permeability