Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig

Joslyn Lay, Simona E. Carbone, Jesse J. Dicello, Nigel Bunnett, Meritxell Canals, Daniel P. Poole

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut function, the cellular and subcellular distribution and regulation of MOR within the enteric nervous system are largely undefined. Herein, we defined the neurochemical coding of MOR-expressing neurons in the guinea pig gut and examined the effects of opioids on MOR trafficking and regulation. MOR expression was restricted to subsets of enteric neurons. In the stomach MOR was mainly localized to nitrergic neurons (~88%), with some overlap with neuropeptide Y (NPY) and no expression by cholinergic neurons. These neurons are likely to have inhibitory motor and secretomotor functions. MOR was restricted to noncholinergic secretomotor neurons (VIP-positive) of the ileum and distal colon submucosal plexus. MOR was mainly detected in nitrergic neurons of the colon (nitric oxide synthase positive, 87%), with some overlap with choline acetyltransferase (ChAT). No expression of MOR by intrinsic sensory neurons was detected. [D-Ala2, MePhe4, Gly(ol)5]enkephalin (DAMGO), morphiceptin, and loperamide induced MOR endocytosis in myenteric neurons. After stimulation with DAMGO and morphiceptin, MOR recycled, whereas MOR was retained within endosomes following loperamide treatment. Herkinorin or the δ-opioid receptor agonist [D-Ala2, D-Leu5]enkephalin (DADLE) did not evoke MOR endocytosis. In summary, we have identified the neurochemical coding of MOR-positive enteric neurons and have demonstrated differential trafficking of MOR in these neurons in response to established and putative MOR agonists.

Original languageEnglish
Pages (from-to)G252-G266
Number of pages15
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume311
Issue number2
DOIs
Publication statusPublished - 1 Aug 2016

Keywords

  • Enteric nervous system
  • G protein-coupled receptor
  • Mu opioid receptor
  • Neurochemical coding
  • Opioid

Cite this

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title = "Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig",
abstract = "The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut function, the cellular and subcellular distribution and regulation of MOR within the enteric nervous system are largely undefined. Herein, we defined the neurochemical coding of MOR-expressing neurons in the guinea pig gut and examined the effects of opioids on MOR trafficking and regulation. MOR expression was restricted to subsets of enteric neurons. In the stomach MOR was mainly localized to nitrergic neurons (~88{\%}), with some overlap with neuropeptide Y (NPY) and no expression by cholinergic neurons. These neurons are likely to have inhibitory motor and secretomotor functions. MOR was restricted to noncholinergic secretomotor neurons (VIP-positive) of the ileum and distal colon submucosal plexus. MOR was mainly detected in nitrergic neurons of the colon (nitric oxide synthase positive, 87{\%}), with some overlap with choline acetyltransferase (ChAT). No expression of MOR by intrinsic sensory neurons was detected. [D-Ala2, MePhe4, Gly(ol)5]enkephalin (DAMGO), morphiceptin, and loperamide induced MOR endocytosis in myenteric neurons. After stimulation with DAMGO and morphiceptin, MOR recycled, whereas MOR was retained within endosomes following loperamide treatment. Herkinorin or the δ-opioid receptor agonist [D-Ala2, D-Leu5]enkephalin (DADLE) did not evoke MOR endocytosis. In summary, we have identified the neurochemical coding of MOR-positive enteric neurons and have demonstrated differential trafficking of MOR in these neurons in response to established and putative MOR agonists.",
keywords = "Enteric nervous system, G protein-coupled receptor, Mu opioid receptor, Neurochemical coding, Opioid",
author = "Joslyn Lay and Carbone, {Simona E.} and Dicello, {Jesse J.} and Nigel Bunnett and Meritxell Canals and Poole, {Daniel P.}",
year = "2016",
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language = "English",
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Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig. / Lay, Joslyn; Carbone, Simona E.; Dicello, Jesse J.; Bunnett, Nigel; Canals, Meritxell; Poole, Daniel P.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 311, No. 2, 01.08.2016, p. G252-G266.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig

AU - Lay, Joslyn

AU - Carbone, Simona E.

AU - Dicello, Jesse J.

AU - Bunnett, Nigel

AU - Canals, Meritxell

AU - Poole, Daniel P.

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KW - G protein-coupled receptor

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