Involvement of enteric nerves in permeability changes due to deoxycholic acid in rat jejunum in vivo.
OBJECTIVE
Stress and Clostridium difficile toxin A increase epithelial permeability in the small intestine via vagus and visceral afferents, in turn activating mucosal mast cells. Bile acids also increase epithelial permeability but it is not known if nerves or mast cells are involved in this effect in the small intestine.


METHODS
In jejunum of anesthetized rats, the effects of hexamethonium and atropine on deoxycholic acid (DCA) induced fluid secretion and increase in epithelial permeability was therefore studied by determining the appearance and disappearance rates of 14C-mannitol and 51Cr-EDTA into and from a perfusion system containing 4 or 8 mm DCA and expressed as clearance.


RESULTS
DCA increased net fluid transport and appearance and to a less extent disappearance rates of the probes. Hexamethonium but not atropine, chronic denervation or the NO synthase inhibitor L-NNA did significantly decrease the appearance rate and net fluid secretion. The levels of the mast cell protease II (RMCP II) in perfusate and plasma were not increased by DCA. The clearance ratio Cr-EDTA/mannitol indicates that the plasma clearance of the permeability probes is partly secondary to net fluid transport only at higher DCA concentrations.


CONCLUSIONS
We conclude that the DCA effect on epithelial permeability is to a large part induced by intramural reflex(es) containing nicotinic receptors. The results also suggest that mast cell degranulation and NO release are not involved in the mechanism. This indicates that the nerve effect on intestinal paracellular permeability is not mediated by the mechanisms described for stress or Clostridium difficile toxin A.
Fihn
B-M
BM
Department of Physiology, University of Göteborg, Göteborg, Sweden.
Sjöqvist
A
A
Jodal
M
M
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D053818:Chymases; D003840:Deoxycholic Acid / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D007421:Intestine, Small / Q000294:innervation* / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000032:analysis
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D003840:Deoxycholic Acid; D019335:Nitroarginine; D018738:Hexamethonium; D001285:Atropine; D019001:Nitric Oxide Synthase; D012697:Serine Endopeptidases; D053818:Chymases