Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport.

Ivana Novak; Susanne Hede; Mette Hansen

doi:10.1007/s00424-007-0403-3

Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport.

Ivana Novak, Susanne Hede, Mette Hansen

Molecular Integrative Physiology

21 Citations (Scopus)

Abstract

Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also express adenosine receptors and whether these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels or Ca(2+)-activated Cl(-) channels and [Formula: see text] transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell adenocarcinoma lines showed that they express A(1), A(2A), A(2B), and A(3) receptors. Real-time PCR revealed relatively low messenger RNA levels of adenosine receptors compared to beta-actin; the rank order for the receptors was A(2A) > A(2B) >/= A(3) >> A(1) for rat pancreas and A(2B) > A(2A) >> A(3) >/= A(1) for duct cell lines. Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about half of the recordings, adenosine depolarized the membrane voltage, and this was because of the opening of Cl(-) channels. Using a Cl(-)-sensitive fluorophore and single-cell imaging on duct cell lines, it was found that 58% of PANC-1 cells responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine elicited Ca(2+) signals only in a few rat and human duct cells, which did not seem to correlate with Cl(-) signals. A(2A) receptors were localized in the luminal membranes of rat pancreatic ducts, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A(2A) receptors open Cl(-) channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini-to-duct signaling.
Udgivelsesdato: 2008-May

Original language	English
Journal	Pflügers Archiv: European Journal of Physiology
Volume	456
Issue number	2
Pages (from-to)	437-447
Number of pages	10
ISSN	0031-6768
DOIs	https://doi.org/10.1007/s00424-007-0403-3
Publication status	Published - 2007

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10.1007/s00424-007-0403-3

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@article{62cb3240179611ddbee902004c4f4f50,

title = "Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport.",

abstract = "Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also express adenosine receptors and whether these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels or Ca(2+)-activated Cl(-) channels and [Formula: see text] transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell adenocarcinoma lines showed that they express A(1), A(2A), A(2B), and A(3) receptors. Real-time PCR revealed relatively low messenger RNA levels of adenosine receptors compared to beta-actin; the rank order for the receptors was A(2A) > A(2B) >/= A(3) >> A(1) for rat pancreas and A(2B) > A(2A) >> A(3) >/= A(1) for duct cell lines. Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about half of the recordings, adenosine depolarized the membrane voltage, and this was because of the opening of Cl(-) channels. Using a Cl(-)-sensitive fluorophore and single-cell imaging on duct cell lines, it was found that 58% of PANC-1 cells responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine elicited Ca(2+) signals only in a few rat and human duct cells, which did not seem to correlate with Cl(-) signals. A(2A) receptors were localized in the luminal membranes of rat pancreatic ducts, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A(2A) receptors open Cl(-) channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini-to-duct signaling. Udgivelsesdato: 2008-May",

author = "Ivana Novak and Susanne Hede and Mette Hansen",

note = "Keywords: Epithelial transport - Adenosine receptor - Adenosine 5-triphosphate (ATP) - Cystic fibrosis - Chloride channel - Pancreatic duct - Bicarbonate transport - Pancreas",

year = "2007",

doi = "10.1007/s00424-007-0403-3",

language = "English",

volume = "456",

pages = "437--447",

journal = "Pfl{\"u}gers Archiv - European Journal of Physiology",

issn = "0031-6768",

publisher = "Springer",

number = "2",

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TY - JOUR

T1 - Adenosine receptors in rat and human pancreatic ducts stimulate chloride transport.

AU - Novak, Ivana

AU - Hede, Susanne

AU - Hansen, Mette

N1 - Keywords: Epithelial transport - Adenosine receptor - Adenosine 5-triphosphate (ATP) - Cystic fibrosis - Chloride channel - Pancreatic duct - Bicarbonate transport - Pancreas

PY - 2007

Y1 - 2007

N2 - Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also express adenosine receptors and whether these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels or Ca(2+)-activated Cl(-) channels and [Formula: see text] transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell adenocarcinoma lines showed that they express A(1), A(2A), A(2B), and A(3) receptors. Real-time PCR revealed relatively low messenger RNA levels of adenosine receptors compared to beta-actin; the rank order for the receptors was A(2A) > A(2B) >/= A(3) >> A(1) for rat pancreas and A(2B) > A(2A) >> A(3) >/= A(1) for duct cell lines. Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about half of the recordings, adenosine depolarized the membrane voltage, and this was because of the opening of Cl(-) channels. Using a Cl(-)-sensitive fluorophore and single-cell imaging on duct cell lines, it was found that 58% of PANC-1 cells responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine elicited Ca(2+) signals only in a few rat and human duct cells, which did not seem to correlate with Cl(-) signals. A(2A) receptors were localized in the luminal membranes of rat pancreatic ducts, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A(2A) receptors open Cl(-) channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini-to-duct signaling. Udgivelsesdato: 2008-May

AB - Previously, we have shown that pancreatic acini release adenosine triphosphate (ATP) and ATP-handling enzymes, and pancreatic ducts express various purinergic P2 receptors. The aim of the present study was to establish whether pancreatic ducts also express adenosine receptors and whether these could be involved in secretory processes, which involve cystic fibrosis transmembrane regulator (CFTR) Cl(-) channels or Ca(2+)-activated Cl(-) channels and [Formula: see text] transporters. Reverse transcriptase polymerase chain reaction analysis on rat pancreatic ducts and human duct cell adenocarcinoma lines showed that they express A(1), A(2A), A(2B), and A(3) receptors. Real-time PCR revealed relatively low messenger RNA levels of adenosine receptors compared to beta-actin; the rank order for the receptors was A(2A) > A(2B) >/= A(3) >> A(1) for rat pancreas and A(2B) > A(2A) >> A(3) >/= A(1) for duct cell lines. Whole-cell patch-clamp recordings on rat pancreatic ducts showed that, in about half of the recordings, adenosine depolarized the membrane voltage, and this was because of the opening of Cl(-) channels. Using a Cl(-)-sensitive fluorophore and single-cell imaging on duct cell lines, it was found that 58% of PANC-1 cells responded to adenosine, whereas only 9% of CFPAC-1 cells responded. Adenosine elicited Ca(2+) signals only in a few rat and human duct cells, which did not seem to correlate with Cl(-) signals. A(2A) receptors were localized in the luminal membranes of rat pancreatic ducts, plasma membrane of many PANC-1 cells, but only a few CFPAC-1 cells. Taken together, our data indicate that A(2A) receptors open Cl(-) channels in pancreatic ducts cells with functional CFTR. We propose that adenosine can stimulate pancreatic secretion and, thereby, is an active player in the acini-to-duct signaling. Udgivelsesdato: 2008-May

U2 - 10.1007/s00424-007-0403-3

DO - 10.1007/s00424-007-0403-3

M3 - Journal article

C2 - 18057956

SN - 0031-6768

VL - 456

SP - 437

EP - 447

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

IS - 2

ER -