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Updated: Jan 27, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
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Quantifying Agonist Activity at G Protein-coupled Receptors

Published on: December 26, 2011

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Agonist-dependent development of delta opioid receptor tolerance in the colon

Jesse J DiCello1,2, Ayame Saito3,4, Pradeep Rajasekhar3,4

  • 1Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia. Jesse.Dicello@Monash.edu.

Cellular and Molecular Life Sciences : CMLS
|March 25, 2019
PubMed

Insights

Delta opioid receptor (DOR) agonists like SNC80 can prolong colonic motor inhibition, potentially causing constipation. ARM390, another DOR agonist, did not affect motor patterns, suggesting fewer gastrointestinal side-effects.

Area of Science:

  • Gastroenterology
  • Neuropharmacology
  • Pain Management

Background:

  • Opioid analgesics cause constipation via mu opioid receptor (MOR) activation in enteric neurons.
  • Delta opioid receptors (DOR) are therapeutic targets for pain, depression, and anxiety.
  • The effect of DOR agonists on colonic transit is not well understood.

Purpose of the Study:

  • To investigate the effects of DOR agonists SNC80 and ARM390 on colonic motility.
  • To examine acute and chronic tolerance to these agonists in neural pathways controlling colonic transit.

Main Methods:

  • Assessed tolerance to SNC80 (full DOR agonist) and ARM390 (partial DOR agonist).
  • Evaluated effects on excitatory and inhibitory pathways in colonic motility.
  • Measured changes in propagating colonic motor patterns after agonist exposure.

Main Results:

  • Excitatory pathways developed acute and chronic tolerance to SNC80; inhibitory pathways showed chronic tolerance.
  • ARM390 exposure did not impair the function of either pathway.
  • SNC80 significantly reduced colonic motor patterns acutely and chronically, unlike ARM390.

Conclusions:

  • SNC80 demonstrates a prolonged inhibitory effect on colonic motility, potentially leading to constipation.
  • ARM390 did not affect colonic motor patterns, indicating a potential for reduced gastrointestinal side-effects.
Keywords:
Colon motilityEndocytosisEnteric nervous systemGPCR regulationOpioid receptor

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