title: Specific localization of β-Arrestin2 in myenteric plexus of mouse gastrointestinal tract.
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.
authors.affiliation: Department of Pharmacology and Toxicology, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Hercules T
authors.initials: HT
authors.lastname: Maguma
authors.affiliation: Department of Pharmacology and Toxicology, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Dipanjana
authors.initials: D
authors.lastname: Datta De
authors.affiliation: Department of Pharmacology and Toxicology, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Sukhada
authors.initials: S
authors.lastname: Bhave
authors.affiliation: Department of Pharmacology and Toxicology, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: William L
authors.initials: WL
authors.lastname: Dewey
authors.affiliation: Department of Pharmacology and Toxicology, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia, United States of America.
authors.forename: Hamid I
authors.initials: HI
authors.lastname: Akbarali
mesh_terms: D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D064032:Calbindin 2 / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009197:Myenteric Plexus / Q000378:metabolism*
chemical_list: D019390:Arrestins; D064032:Calbindin 2; D002795:Choline O-Acetyltransferase
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