The effect of morphine on mast cell-mediated mucosal permeability.
BACKGROUND
The late phase of post-traumatic multisystem organ failure is associated with sepsis from organisms that normally reside within the gut's lumen. Morphine, a commonly employed analgesic in injured patients, is associated with intestinal stasis, bacterial overgrowth, and translocation when administered to rats. N-formyl-methionyl-leucyl-phenylalanine (FMLP), a toxic product of gram-negative organisms, provokes an increase in mucosal permeability when infused into the ileal lumen of this species. The current study was designed to examine the effects of morphine on FMLP perturbation of the mucosal barrier of the ileum of rats and mice to an impermeant macromolecule, dextran 4400. The potential role of mucosal mast cells in the response to either agent alone or in combination was examined.


METHODS
Intact and isolated segments of distal ileum of naïve and sensitized (Trichinella spiralis and egg albumin) Sprague-Dawley rats were exposed to FMLP with or without morphine or doxantrazole, a mast cell-stabilizing agent. Isolated segments of distal ileum of mast cell-deficient mice also were studied.


RESULTS
Mucosal exposure of distal ileal mucosa (intact and isolated, and naive and sensitized) to FMLP was associated with an increase in permeability to dextran 4400, which was completely ablated by morphine and doxantrazole. Sensitization was associated with a prolongation of the FMLP response. Ilea of mast cell-deficient mice (but not their wild type litter mates) were unresponsive to FMLP.


CONCLUSIONS
Morphine antagonizes the provocative effect of FMLP on the mucosal barrier to dextran 4400 of the ilea of rats and mice. Intestinal mucosal mast cells play a central role in the process.
Harari
Yael
Y
Departments of Surgery, Integrative Biology and Pharmacology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
Weisbrodt
Norman W
NW
Moody
Frank G
FG
D000588:Amines / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003911:Dextrans / Q000493:pharmacokinetics; D007082:Ileum / Q000378:metabolism*; D007114:Immunization; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009020:Morphine / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D051381:Rats / Q000276:immunology / Q000469:parasitology; D017207:Rats, Sprague-Dawley; D013892:Thioxanthenes / Q000494:pharmacology; D017160:Trichinella spiralis / Q000276:immunology; D044004:Xanthones / Q000494:pharmacology
D000588:Amines; D000701:Analgesics, Opioid; D016207:Cytokines; D003911:Dextrans; D013892:Thioxanthenes; D044004:Xanthones; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine; C010134:doxantrazole