Inflammation enhances mu-opioid receptor transcription and expression in mice intestine

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 mu-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 mu-OR mRNA determined by a competitive reverse-transcriptase polymerase chain reaction; the levels of mu-OR protein by Western blot immunoassay, and the localization and number of cells expressing mu-OR using immunohistochemistry. The results show a significant increase of mu-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 mu-OR immunoreactivity in the myenteric plexus but not in the submucosal plexus. Our results show that intestinal inflammation enhances the transcription and translation of mu-OR mRNA, thus explaining the increased potency of mu-opioids during inflammation.