Specific Localization of β-Arrestin2 in Myenteric Plexus of Mouse Gastrointestinal Tract

Authors

Hercules T. Maguma, Virginia Commonwealth University
Dipanjana D. De, Virginia Commonwealth University
Sukhada Bhave, Virginia Commonwealth University
William L. Dewey, Virginia Commonwealth University
Hamid I. Akbarali, Virginia Commonwealth UniversityFollow

Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

PLOS ONE

Volume

9

DOI of Original Publication

10.1371/journal.pone.0103894

Comments

Originally Published at http://dx.doi.org/10.1371/journal.pone.0103894

Date of Submission

November 2014

Abstract

Abstract

β-arrestin2 is a key molecule involved in signaling and internalization of activated G protein-coupled receptors including µ-opioid receptors (MOR). Previously we have shown that decreased expression of β-arrestin2 upon chronic morphine is associated with the development of opioid tolerance in the gastrointestinal tract. However, the localization of β-arrestin2 within the gastrointestinal wall is not known. In this study we found that β-arrestin2 is localized in the soma of a select group of neurons in the myenteric ganglia but not in smooth muscle. The density of β-arestin2 was significantly higher in the ileum than the colon. We identified four variants of β-arrestin2 in the ileum, with ARRB-005 and ARRB-013 being the most abundant. Further, the current study utilized multiple-labeling immunofluorescence to characterize the chemical coding of neurons expressing β-arrestin2 in the murine myenteric plexus and the co-localization of MOR1 and β-arrestin2. β-arrestin2 co-localized with choline acetyltransferase and calretinin. In contrast, β-arrestin2 neither co-localized with substance P, nitric oxide synthase nor calbindin. Genetic deletion of β-arrestin2 did not affect cholinergic neuron activation by nicotine in the isolated ileum (-log M EC50: wild type = 5.8 vs. β-arrestin2 knockout = 5.9). Our findings suggest specificity in the localization of β-arrestin2 in the myenteric plexus within MOR1-expressing neurons and provide a relation for direct intracellular crosstalk between MOR1 receptor activation and β-arrestin2 signaling in the myenteric neurons. β-arrestin2 deletion does not directly alter basal enteric cholinergic neuronal function.

Rights

Copyright: © 2014 Maguma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Pharmacology and Toxicology Publications