Expression of Adenosine Receptors in Rodent Pancreas.

Hayashi Hayashi

doi:10.3390/ijms20215329

Abstract

Adenosine regulates exocrine and endocrine secretions in the pancreas. Adenosine is considered to play a role in acini-to-duct signaling in the exocrine pancreas. To identify the molecular basis of functional adenosine receptors in the exocrine pancreas, immunohistochemical analysis was performed in the rat, mouse, and guinea pig pancreas, and the secretory rate and concentration of HCO3− in pancreatic juice from the rat pancreas were measured. The A2A adenosine receptor colocalized with ezrin, an A-kinase anchoring protein, in the luminal membrane of duct cells in the mouse and guinea pig pancreas. However, a strong signal ascribed to A2B adenosine receptors was detected in insulin-positive β cells in islets of Langerhans. The A2A adenosine receptor agonist 4-[2-[[6-Amino-9-(N-ethyl-β-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid (CGS 21680) stimulated HCO3−-rich fluid secretion from the rat pancreas. These results indicate that A2A adenosine receptors may be, at least in part, involved in the exocrine secretion of pancreatic duct cells via acini-to-duct signaling. The adenosine receptors may be a potential therapeutic target for cancer as well as exocrine dysfunctions of the pancreas.

Highlights

The pancreas performs both exocrine and endocrine functions
In order to determine the cells that expressed A2A and A2B adenosine receptors, triple staining of adenosine receptors was performed with insulin and glucagon on paraffin sections of the rat pancreas
This conclusion was based on the following major results: the A2A adenosine receptor agonist stimulated a HCO3−-rich fluid secretion from the rat pancreas (Figure 6A–C); the A2A adenosine receptor colocalized with ezrin in the luminal membrane of duct cells in the mouse and guinea pig pancreas (Figures 3 and 4), as reported in rats previously

Summary

Introduction

The pancreas performs both exocrine and endocrine functions. Pancreatic acini secrete digestive enzyme- and Cl−-rich neutral fluid, and ducts secrete an HCO3−-rich pancreatic juice that neutralizes acidic chyme in the duodenum. Islets of Langerhans are involved in maintaining glucose homeostasis and comprise α-, β-, γ-, δ-, and ε-cells, which secrete glucagon, insulin and amylin, pancreatic polypeptide, somatostatin, and ghrelin, respectively [5]. Both exocrine and endocrine cells are regulated by nucleotides, as well as parasympathetic and sympathetic nerves and hormones [6]. Adenosine activates Cl− conductance in pancreatic duct cells of the rat and guinea pig [8,9]. N6-L-phenyl-isopropyl-adenosine, an A1 adenosine receptor agonist, reduced glucose-induced insulin secretion from the perfused rat and mouse pancreas [11,12,13]. Adenosine at 100 μM augmented insulin secretion through the

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Results

Conclusion