Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells

1988 ◽  
Vol 105 (2) ◽  
pp. 131-142 ◽  
Author(s):  
M. A. Gray ◽  
J. R. Greenwell ◽  
B. E. Argent
Keyword(s):  
Plasma Membrane ◽  
Pancreatic Duct ◽  
Chloride Channel ◽  
Apical Plasma Membrane ◽  
Duct Cells ◽  
Pancreatic Duct Cells

cAMP-regulated whole cell chloride currents in pancreatic duct cells

1993 ◽  
Vol 264 (3) ◽  
pp. C591-C602 ◽  
Author(s):  
M. A. Gray ◽  
S. Plant ◽  
B. E. Argent
Keyword(s):  
Pancreatic Duct ◽  
Single Cells ◽  
Duct Cell ◽  
Disulfonic Acid ◽  
Apical Plasma Membrane ◽  
Patch Clamp Technique ◽  
Chloride Currents ◽  
Whole Cell ◽  
Duct Cells ◽  
Pancreatic Duct Cells

Using the whole cell configuration of the patch-clamp technique, we have identified an adenosine 3',5'-cyclic monophosphate (cAMP)-regulated chloride conductance in pancreatic duct cells. Basal whole cell currents in single isolated cells were very low (approximately 5 pA/pF) but could be stimulated 17-fold by elevation of intracellular cAMP. The cAMP-activated currents exhibited 1) a high chloride selectivity, 2) a near linear current-voltage relationship, 3) time and voltage independence, 4) block by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) but not by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and 5) an anion selectivity sequence based on permeability ratios of SCN > NO3 > Br > Cl > I > HCO3 > F > ClO4 > gluconate. Currents in single cells ran down within a few minutes; however, stable chloride currents could be recorded from duct cell clusters in which four or five cells were in electrical communication. We present evidence suggesting that these cAMP-regulated currents are carried by cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. Physiologically, these CFTR channels act in parallel with chloride-bicarbonate exchangers to facilitate bicarbonate secretion across the apical plasma membrane of the duct cell.

scholarly journals Bile Acids Selectively Activate Iberiotoxin-sensitive Potassium Channels In Native Pancreatic Duct Cells

2009 ◽  
Vol 96 (3) ◽  
pp. 536a-537a
Author(s):  
Viktoria Venglovecz ◽  
Peter Hegyi ◽  
Zoltan Rakonczay ◽  
Barry Argent ◽  
Michael A. Gray
Keyword(s):  
Potassium Channels ◽  
Pancreatic Duct ◽  
Bile Acids ◽  
Duct Cells ◽  
Pancreatic Duct Cells

scholarly journals Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3

2002 ◽  
Vol 159 (2) ◽  
pp. 303-312 ◽  
Author(s):  
Yves Heremans ◽  
Mark Van De Casteele ◽  
Peter in't Veld ◽  
Gerard Gradwohl ◽  
Palle Serup ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Pancreatic Duct ◽  
Endocrine Pancreas ◽  
Notch Pathway ◽  
Neuroendocrine Differentiation ◽  
Β Cell ◽  
Neurogenin 3 ◽  
Adult Human ◽  
Duct Cells ◽  
Pancreatic Duct Cells

Regulatory proteins have been identified in embryonic development of the endocrine pancreas. It is unknown whether these factors can also play a role in the formation of pancreatic endocrine cells from postnatal nonendocrine cells. The present study demonstrates that adult human pancreatic duct cells can be converted into insulin-expressing cells after ectopic, adenovirus-mediated expression of the class B basic helix-loop-helix factor neurogenin 3 (ngn3), which is a critical factor in embryogenesis of the mouse endocrine pancreas. Infection with adenovirus ngn3 (Adngn3) induced gene and/or protein expression of NeuroD/β2, Pax4, Nkx2.2, Pax6, and Nkx6.1, all known to be essential for β-cell differentiation in mouse embryos. Expression of ngn3 in adult human duct cells induced Notch ligands Dll1 and Dll4 and neuroendocrine- and β-cell–specific markers: it increased the percentage of synaptophysin- and insulin-positive cells 15-fold in ngn3-infected versus control cells. Infection with NeuroD/β2 (a downstream target of ngn3) induced similar effects. These data indicate that the Delta-Notch pathway, which controls embryonic development of the mouse endocrine pancreas, can also operate in adult human duct cells driving them to a neuroendocrine phenotype with the formation of insulin-expressing cells.

scholarly journals Differentiation of Affinity-Purified Human Pancreatic Duct Cells to  -Cells

Diabetes ◽  
2007 ◽  
Vol 56 (7) ◽  
pp. 1802-1809 ◽  
Author(s):  
S. Yatoh ◽  
R. Dodge ◽  
T. Akashi ◽  
A. Omer ◽  
A. Sharma ◽  
...  
Keyword(s):  
Pancreatic Duct ◽  
Duct Cells ◽  
Pancreatic Duct Cells

Downregulated in adenoma and putative anion transporter are regulated by CFTR in cultured pancreatic duct cells

2001 ◽  
Vol 281 (5) ◽  
pp. G1301-G1308 ◽  
Author(s):  
Tracy Greeley ◽  
Holli Shumaker ◽  
Zhaohui Wang ◽  
Clifford W. Schweinfest ◽  
Manoocher Soleimani
Keyword(s):  
Pancreatic Duct ◽  
Northern Hybridization ◽  
Transmembrane Conductance Regulator ◽  
Duct Cells ◽  
Anion Transporter ◽  
Pancreatic Duct Cells ◽  
Cf Transmembrane Conductance Regulator ◽  
Immunohistochemical Studies ◽  
Exchange Activity ◽  
In Cells

The mechanism of the pancreatic ductal HCO[Formula: see text] secretion defect in cystic fibrosis (CF) is not well defined. However, a lack of apical Cl−/HCO[Formula: see text] exchange may exist in CF. To test this hypothesis, we examined the expression of Cl−/HCO[Formula: see text] exchangers in cultured pancreatic duct epithelial cells with physiological features prototypical of CF [CFPAC-1 cells lacking a functional CF transmembrane conductance regulator (CFTR)] or normal duct cells (CFPAC-1 cells transfected with functional wild-type CFTR, CFPAC-WT). Cl−/HCO[Formula: see text] exchange activity, assayed with the pH-sensitive dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in cells grown on coverslips, increased about twofold in cells transfected with functional CFTR. This correlated with increased apical 36Cl influx in cells expressing functional CFTR and grown on permeable support. Northern hybridizations indicated the induction of downregulated in adenoma (DRA) in cells expressing functional CFTR. The expression of putative anion transporter PAT1 also increased significantly in cells expressing functional CFTR. DRA was detected at high levels in native mouse pancreas by Northern hybridization and localized to the apical domain of the duct cells by immunohistochemical studies. In conclusion, CFTR upregulates DRA and PAT1 expression in cultured pancreatic duct cells. We propose that the pancreatic HCO[Formula: see text] secretion defect in CF patients is partly due to the downregulation of apical Cl−/HCO[Formula: see text] exchange activity mediated by DRA (and possibly PAT1).

Genetic instability in grossly normal pancreatic duct cells from patients with chronic pancreatitis and pancreatic cancer

2000 ◽  
Vol 118 (4) ◽  
pp. A196
Author(s):  
Alyssa M. Brown ◽  
Mary P. Bronner ◽  
Teri Brentnall ◽  
Peter S. Rabinovitch ◽  
Katie R. Carter ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Pancreatic Duct ◽  
Genetic Instability ◽  
Duct Cells ◽  
Pancreatic Duct Cells
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