The expression of delta- and kappa-opioid receptor is enhanced during intestinal inflammation in mice

Abstract

In the gut, mu-, delta-, and kappa-opioid receptors are present in the submucous and myenteric plexi and in enterocytes. Using pharmacological methods, our group has shown that intestinal inflammation enhances the antitransit and antisecretory effects of systemic opioids. The aim of the present study was to evaluate whether the enhanced antisecretory effects of delta and kappa-agonists were associated with an increased transcription and/or expression of these receptors at central (brain and spinal cord) and/or peripheral sites (gut); we also evaluated the expression of delta- and kappa-opioid receptors in dissected sections of the gut containing the myenteric (MP/LM) or submucous (SP/M) plexi. The mRNA and protein levels of both opioid receptors were determined using a reverse-transcriptase polymerase chain reaction and immunoprecipitation/Western blot, respectively. Intestinal inflammation significantly augmented the transcription of delta-opioid receptors in the spinal cord (34%) and in the whole gut (102%). Also increased mRNA and protein levels of delta-opioid receptors in the MP/LM and SP/M preparations. The kappa-opioid receptors gene transcription was not altered by inflammation, whereas kappa-opioid receptors protein levels were significantly enhanced in the SP/M preparation. No changes in gene transcription or protein levels for delta- and kappa-opioid receptors could be demonstrated in the brain. These results suggest that local transcriptional and post-transcriptional changes of the delta- and kappa-opioid receptors genes could be responsible for the enhanced antisecretory effects of delta- and kappa-opioid agonists during intestinal inflammation.