Abstract
In the gut, μ-, δ-, and κ-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 δ and κ-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 δ- and κ-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 δ-opioid receptors in the spinal cord (34%) and in the whole gut (102%). Also increased mRNA and protein levels of δ-opioid receptors in the MP/LM and SP/M preparations. The κ-opioid receptors gene transcription was not altered by inflammation, whereas κ-opioid receptors protein levels were significantly enhanced in the SP/M preparation. No changes in gene transcription or protein levels for δ- and κ-opioid receptors could be demonstrated in the brain. These results suggest that local transcriptional and post-transcriptional changes of the δ- and κ-opioid receptors genes could be responsible for the enhanced antisecretory effects of δ- and κ-opioid agonists during intestinal inflammation.
Footnotes
-
This work was supported by grants from FIS (00/0658) and CICYT (PM980155), Madrid and Generalitat de Catalunya (2001SGR00409), Barcelona, Spain. Part of these results have been presented as a communication to the 31th Annual Meeting Society for Neuroscience (San Diego, CA) on November 10–15, 2001.
-
DOI: 10.1124/jpet.103.049346.
-
ABBREVIATIONS: MP/LM, circular muscle layers-myenteric plexus-longitudinal muscle; SP/M, submucosal plexus-mucosa; RT, reverse transcriptase; PCR, polymerase chain reaction; PBS, phosphate-buffered saline; bp, base pair; ANOVA, analysis of variance; U-50488H, (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide.
- Received January 29, 2003.
- Accepted April 16, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|