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Aim: To study the effect of the opioid-receptor like-1 (ORL1) agonist nociceptin on gastrointestinal (GI) myenteric neurotransmission and motility.
Methods: Reverse transcriptase - polymerase chain reaction and immunohistochemistry were used to localize nociceptin and ORL1 in mouse tissues. Intracellular electrophysiological recordings of excitatory and inhibitory junction potentials (EJP, IJP) were made in a chambered organ bath. Intestinal motility was measured in vivo.
Results: Nociceptin accelerated whole and upper GI transit, but slowed colonic expulsion in vivo in an ORL1-dependent manner, as shown using [Nphe(1)]NOC and AS ODN pretreatment. ORL1 and nociceptin immunoreactivity were found on enteric neurons. Nociceptin reduced the EJP and the nitric oxide-sensitive slow IJP in an ORL1-dependent manner, whereas the fast IJP was unchanged. Nociceptin further reduced the spatial spreading of the EJP up to 2 cm.
Conclusion: Compounds acting at ORL1 are good candidates for the future treatment of disorders associated with increased colonic transit, such as diarrhea or diarrhea-predominant irritable bowel syndrome.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526842 | PMC |
| http://dx.doi.org/10.4292/wjgpt.v6.i3.73 | DOI Listing |
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