Inflammation Enhances μ-Opioid Receptor Transcription and Expression in Mice Intestine
- 1Anesthesiology Research Unit, Institut Municipal InvestigacióMèdica, Department of Anesthesiology, Hospital Universitario del Mar, Barcelona, Spain (O.P., M.M.P.); 2Department of Pathology, Hospital Universitario del Mar, Barcelona, Spain (F.A.)
- Olga Pol, Ph.D., Anesthesiology Research Unit, Institut Municipal Investigació Mèdica, Doctor Aiguader, 80, 08003 Barcelona, Spain. E-mail: opol{at}imim.es
Abstract
Opioid receptors (ORs) and their mRNA are present in the central and peripheral nervous systems of mammals and in different peripheral tissues, including the gut. Using a model of croton oil-induced (CO) intestinal inflammation in mice, we have shown a 6-fold increase in the potency of the antitransit and antisecretory effects of μ-OR agonists, mediated by peripheral ORs. We postulate that the enhanced effects are mediated by an increase in the expression of intestinal OR. We used jejunum (stripped of the mucosal layer) from mice with CO-induced intestinal inflammation and, as control subjects, saline-treated animals (SS). We evaluated the quantity of μ-OR mRNA determined by a competitive reverse-transcriptase polymerase chain reaction; the levels of μ-OR protein by Western blot immunoassay, and the localization and number of cells expressing μ-OR using immunohistochemistry. The results show a significant increase of μ-OR mRNA (7.7-fold) and receptor protein (3-fold) during intestinal inflammation. Inflammation also induced a 64.3% increase in the number of neurons expressing μ-OR immunoreactivity in the myenteric plexus but not in the submucosal plexus. Our results show that intestinal inflammation enhances the transcription and translation of μ-OR mRNA, thus explaining the increased potency of μ-opioids during inflammation.
Footnotes
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This work was supported by Fondo de Investigaciones Sanitarias Grant 00/0658 and Comisión Interministerial de Ciencia y Tecnologica Grant PM98–0155, Madrid and Fundació La Maratóde TV3 Grant 2032/97, Barcelona, Spain. These results have been presented in part as communications to the 29th Annual Meeting Society for Neuroscience (October 1999, Miami, FL) and the 30th Annual Meeting Society for Neuroscience (November 2000, New Orleans, LA).
- Abbreviations:
- OR
- opioid receptor
- PCR
- polymerase chain reaction
- SS
- saline
- RT
- reverse transcriptase
- bp
- base pair(s)
- CO
- croton oil
- PAGE
- polyacrylamide gel electrophoresis
- PBS
- phosphate-buffered saline
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- Received February 8, 2001.
- Accepted July 12, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
