Effects of mu-opioid receptor agonists on intestinal secretion and permeability during acute intestinal inflammation in mice.
We evaluated and compared the effects of mu-opioid receptor agonists on mucosal fluid transport and permeability, during acute intestinal inflammation. We hypothesized that inflammation would sensitize mu-opioid receptors in the submucosal plexus and/or enterocytes enhancing the effects of mu-opioid receptor agonists. Inflammation was induced by intragastric administration of croton oil, whereas controls received saline. Fluid transport was assessed by enteropooling, and intestinal permeability by blood-to-lumen passage of [51Cr] etylenediaminetetraacetate ([51Cr] EDTA). Intestinal inflammation induced a significant increase in enteropooling (1.9 times) and permeability (2.5 times). In saline- and croton oil-treated animals, mu-opioid receptor agonists produced dose-related inhibitions of enteropooling and intestinal permeability. During inflammation, the potency of morphine increased 4.8 and 3.7 times, inhibiting enteropooling and intestinal permeability, respectively; the potencies of fentanyl and PL017 similarly increased by approximately three (enteropooling) and two times (permeability) in croton oil animals. All effects were reversed by naloxone and naloxone methiodide. The results show that inflammation increases the inhibitory potency of mu-opioid receptor agonists on secretion and permeability, suggesting a sensitization of peripheral mu-opioid receptors.
Valle
L
L
Anesthesiology Research Unit, Institut Municipal Investigació Mèdica, Department of Anesthesiology, Hospital Universitario del Mar, C/ Dr Aiguader, 80, 08003, Barcelona, Spain.
Puig
M M
MM
Pol
O
O
D000208:Acute Disease; D000818:Animals; D003436:Croton Oil / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000494:pharmacology; D004751:Enteritis / Q000378:metabolism*; D005283:Fentanyl / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010539:Permeability; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors
D004723:Endorphins; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; D003436:Croton Oil; C044708:morphiceptin, N-Me-Phe(3)-; D005283:Fentanyl