| First Author | Maguma HT | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 8 | Pages | e103894 |
| PubMed ID | 25083714 | Mgi Jnum | J:223170 |
| Mgi Id | MGI:5648158 | Doi | 10.1371/journal.pone.0103894 |
| Citation | Maguma HT, et al. (2014) Specific localization of beta-Arrestin2 in myenteric plexus of mouse gastrointestinal tract. PLoS One 9(8):e103894 |
| abstractText | beta-arrestin2 is a key molecule involved in signaling and internalization of activated G protein-coupled receptors including micro-opioid receptors (MOR). Previously we have shown that decreased expression of beta-arrestin2 upon chronic morphine is associated with the development of opioid tolerance in the gastrointestinal tract. However, the localization of beta-arrestin2 within the gastrointestinal wall is not known. In this study we found that beta-arrestin2 is localized in the soma of a select group of neurons in the myenteric ganglia but not in smooth muscle. The density of beta-arestin2 was significantly higher in the ileum than the colon. We identified four variants of beta-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 beta-arrestin2 in the murine myenteric plexus and the co-localization of MOR1 and beta-arrestin2. beta-arrestin2 co-localized with choline acetyltransferase and calretinin. In contrast, beta-arrestin2 neither co-localized with substance P, nitric oxide synthase nor calbindin. Genetic deletion of beta-arrestin2 did not affect cholinergic neuron activation by nicotine in the isolated ileum (-log M EC50: wild type = 5.8 vs. beta-arrestin2 knockout = 5.9). Our findings suggest specificity in the localization of beta-arrestin2 in the myenteric plexus within MOR1-expressing neurons and provide a relation for direct intracellular crosstalk between MOR1 receptor activation and beta-arrestin2 signaling in the myenteric neurons. beta-arrestin2 deletion does not directly alter basal enteric cholinergic neuronal function. |
