title: The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells.
abstract: Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl(-) channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (V te) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 μM, which corresponded to the value obtained on whole-cell Cl(-) currents in Capan-1 single cells. The effects of adenosine on V te, an equivalent short-circuit current (I sc), and whole-cell Cl(-) currents were inhibited by CFTRinh-172, a cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel inhibitor. The adenosine A2B receptor agonist, BAY 60-6583, increased I sc and whole-cell Cl(-) currents through CFTR Cl(-) channels, whereas the A2A receptor agonist, CGS 21680, had negligible effects. The A2B receptor antagonist, PSB 603, inhibited the response of I sc to adenosine. Immunohistochemical analysis showed that the A2A and A2B receptors colocalized with Ezrin in the luminal membranes of Capan-1 monolayers and in rat pancreatic ducts. Adenosine elicited the whole-cell Cl(-) currents in guinea pig duct cells. These results demonstrate that luminal adenosine regulates anion secretion by activating CFTR Cl(-) channels via adenosine A2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion.
authors.affiliation: Department of Physiology, Kansai Medical University, 2-5-1 Shimmachi, Hirakata, 573-1010, Japan. hayashmi@hirakata.kmu.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Medical Research Project, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Inagaki
authors.affiliation: Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, August Krogh Building, Universitetsparken 13, 2100, Copenhagen Ø, Denmark.
authors.forename: I
authors.initials: I
authors.lastname: Novak
authors.affiliation: Department of Physiology, Kansai Medical University, 2-5-1 Shimmachi, Hirakata, 573-1010, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D014529:Uridine / Q000494:pharmacology
chemical_list: C531194:4-(2-(5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-carboxamido)ethylamido)benzylphosphonic acid diethyl ester; D000631:Aminopyridines; D000838:Anions; C518875:BAY 60-6583; D002712:Chlorides; D010627:Phenethylamines; D043704:Receptor, Adenosine A2B; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000241:Adenosine; D014529:Uridine
keywords: Adenosine receptor; CFTR; Cl− channel; Duct; Pancreas