The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

M. Hayashi; A. Inagaki; Ivana Novak; H. Matsuda

doi:10.1007/s00424-016-1806-9

The adenosine A_2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

M. Hayashi^*, A. Inagaki, Ivana Novak, H. Matsuda

^*Corresponding author for this work

Cell Biology and Physiology

8 Citations (Scopus)

57 Downloads (Pure)

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 A_2B receptor agonist, BAY 60-6583, increased I_sc and whole-cell Cl⁻ currents through CFTR Cl⁻ channels, whereas the A_2A receptor agonist, CGS 21680, had negligible effects. The A_2B receptor antagonist, PSB 603, inhibited the response of I_sc to adenosine. Immunohistochemical analysis showed that the A_2A and A_2B 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 A_2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion.

Original language	English
Journal	Pfluegers Archiv
Volume	468
Issue number	7
Pages (from-to)	1171-1181
Number of pages	11
ISSN	0031-6768
DOIs	https://doi.org/10.1007/s00424-016-1806-9
Publication status	Published - 1 Jul 2016

Keywords

Adenosine receptor
CFTR
Cl channel
Duct
Pancreas

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Cite this

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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 (Vte) 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 Vte, an equivalent short-circuit current (Isc), 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 Isc 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 Isc 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.",

keywords = "Adenosine receptor, CFTR, Cl channel, Duct, Pancreas",

author = "M. Hayashi and A. Inagaki and Ivana Novak and H. Matsuda",

year = "2016",

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TY - JOUR

T1 - The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

AU - Hayashi, M.

AU - Inagaki, A.

AU - Novak, Ivana

AU - Matsuda, H.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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 (Vte) 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 Vte, an equivalent short-circuit current (Isc), 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 Isc 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 Isc 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.

AB - 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 (Vte) 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 Vte, an equivalent short-circuit current (Isc), 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 Isc 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 Isc 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.

KW - Adenosine receptor

KW - CFTR

KW - Cl channel

KW - Duct

KW - Pancreas

U2 - 10.1007/s00424-016-1806-9

DO - 10.1007/s00424-016-1806-9

M3 - Journal article

C2 - 26965147

AN - SCOPUS:84960419899

SN - 0031-6768

VL - 468

SP - 1171

EP - 1181

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

IS - 7

ER -