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

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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
OriginalsprogEngelsk
TidsskriftPflügers Archiv: European Journal of Physiology
Vol/bind456
Udgave nummer2
Sider (fra-til)437-447
Antal sider10
ISSN0031-6768
DOI
StatusUdgivet - 2007

ID: 3925825