Expression of Adenosine A2B Receptor and Adenosine Deaminase in Rabbit Gastric Mucosa ECL Cells.

Rosa María Arin,Ana Isabel Vallejo,Olatz Fresnedo,Begoña Ochoa,Yuri Rueda

doi:10.3390/molecules22040625

Rosa María Arin, Ana Isabel Vallejo + Show 3 more

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https://doi.org/10.3390/molecules22040625

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Abstract

Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal cells through A2B adenosine receptor (A2BR) binding. A functional link between surface A2BR and adenosine deaminase (ADA) was found in parietal cells, but whether this connection is a general feature of gastric mucosa cells is unknown. Here we examine whether A2BR is expressed at the membrane of histamine-producing enterochromaffin-like (ECL) cells, the major endocrine cell type in the oxyntic mucosa, and if so, whether it has a vicinity relationship with ADA. We used a highly homogeneous population of rabbit ECL cells (size 7.5–10 µm) after purification by elutriation centrifugation. The surface expression of A2BR and ADA proteins was assessed by flow cytometry and confocal microscopy. Our findings demonstrate that A2BR and ADA are partially coexpressed at the gastric ECL cell surface and that A2BR is functional, with regard to binding of adenosine analogs and adenylate cyclase activation. The physiological relevance of A2BR and ADA association in regulating histamine release is yet to be explained.

Highlights

Adenosine (Ado) is a regulatory metabolite that modulates a broad spectrum of processes in many cells of the gastrointestinal tract [1,2]
The ECL cell of the oxyntic mucosa plays a critical role in the regulation of acid secretion through the production and secretion of histamine
ECL cells respond to gastrin by releasing histamine and to somatostatin by inhibiting histamine release

Summary

Introduction

Adenosine (Ado) is a regulatory metabolite that modulates a broad spectrum of processes in many cells of the gastrointestinal tract [1,2]. Ado is continuously produced in intracellular and extracellular locations. In healthy, unstressed tissues, extracellular Ado has a very short-life due to a compensation of concentrations between the extra and the intracellular compartments, which is mainly achieved via equilibrative nucleoside transporters (ENTs) and a rapid metabolism. The Ado basal levels in the interstitial fluid are between 30 and 300 nM [3]. Under pathophysiological conditions, such as metabolic stress or during inflammation-associated tissue hypoxia or ischemia, Ado generation can exceed the removal capacity resulting in markedly increased extracellular concentrations [4]. Uncontrolled release from cells with damaged plasma membranes—such as that resulting from mechanical stress or trauma— provides large increases of extracellular purine nucleosides and nucleotides (ATP levels in cells are typically 3–5 mM). ATP is a cotransmitter [2,5] and this phenomenon is evident in enteric nerves (excellent reviews can be found in references [2,6])

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