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Am J Physiol Gastrointest Liver Physiol 281: G8-G15, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 1, G8-G15, July 2001

THEME
Receptors and Transmission in the Brain-Gut Axis: Potential for Novel Therapies
III. µ-Opioid receptors in the enteric nervous system

Catia Sternini

CURE Digestive Diseases Research Center, Department of Veterans Affairs Greater Los Angeles Healthcare System, Digestive Diseases Division, Departments of Medicine and Neurobiology, University of California, Los Angeles, California 90095

G protein-coupled receptors are cell surface signal-transducing proteins, which elicit a variety of biological functions by the activation of different intracellular effector systems. Many of these receptors, including the µ-opioid receptor (µOR), have been localized in the gastrointestinal tract. µOR is the target of opioids and alkaloids, potent analgesic drugs with high potential for abuse. µOR is expressed by enteric neurons, and it undergoes ligand-selective endocytosis. It is of clinical importance because it mediates tolerance and other major side effects of opiate analgesics, including impairment of gastrointestinal propulsion. An important observation of µOR is its differential trafficking and desensitization properties in response to individual agonists, which might have long-term physiological consequences and be involved in the development of opiate side effects. Receptor activation by agonists is the basis for signaling, and alterations of the mechanisms controlling cellular responses of G protein-coupled receptors to agonists might be the basis of several diseases, including gastrointestinal diseases. Therefore, understanding these basic cellular mechanisms is important for developing appropriate therapeutic agents.

G protein-coupled receptors; receptor endocytosis; motoneurons; receptor trafficking


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