| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Internal Medicine, University of Cincinnati, Cincinnati 45267; 3 Veterans Affairs Medical Center, Cincinnati, Ohio 45220; and 2 Center for Molecular and Structural Biology, Medical University of South Carolina, Charleston, South Carolina 29425
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The mechanism of the
pancreatic ductal HCO
/HCO/HCO/HCO/HCO
cystic fibrosis; HCO
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THE EXCRETORY
DUCT SYSTEM of the pancreas serves as a conduit for delivery of
an alkaline, HCO
Cystic fibrosis (CF), which is an autosomal recessive disease and
results from mutational inactivation of a cAMP-sensitive Cl channel, manifests itself with impairments in the
respiratory, pancreatic, hepatobiliary, and genitourinary systems
(27). The pancreatic dysfunction is felt to result
primarily from impairment of secretin-stimulated ductal
Cl and HCO
The currently accepted model of pancreatic ductal
HCO into the lumen. The resultant increases in luminal
Cl then drive an apical
Cl/HCO
Recent studies from our laboratory (31) suggested that
1) HCO secretion. It was proposed that the
defect in agonist-stimulated ductal HCO
Studies (20) in perfused pancreatic ducts indicated a
decrease in apical Cl/HCO/HCO/base exchangers.
These transporters have a distinct and limited tissue expression
pattern and share no significant homology to AEs. Three members of this
family, downregulated in adenoma (DRA or SLC26A3), pendrin (PDS or
SLC26A4), and the putative anion transporter (PAT1 or SLC26A6), are
located on the apical domain of epithelial cells (11, 13, 14, 22,
23, 30, 37). Functional studies have demonstrated that DRA and
pendrin are actually Cl/HCO/HCO
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Cell lines.
CFPAC-1, a pancreatic duct cell line derived from a patient with CF and
bearing a 
F508 mutation, was cultured as previously described
(29, 31). Stably transfected CFPAC-1 cells bearing functional CFTR (termed CFPAC-WT) were generous gifts from Dr. Raymond
Frizzell and were cultured in a similar fashion except for the addition
of G418 (1 mg/ml) to the medium (31). Two independent CFPAC-1 clones (obtained in our laboratory) and two other CFPAC-WT clones (gifts from Dr. Frizzell) were further tested to verify the results.
Cell pH measurement.
Changes in intracellular pH (pHi) were monitored using the
acetoxymethyl ester of the pH-sensitive fluorescent dye
2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF-AM) as described previously (3, 4, 38). Cells were grown to confluence on glass coverslips and incubated in the presence of 5 µM BCECF in a solution consisting of 115 mM tetramethylammonium (TMA) Cl (or NaCl), 25 mM 1KHCO
/HCO-containing
solution that consisted of 115 mM NaCl and 25 mM
NaHCO-free medium (115 mM Na gluconate and 25 mM
NaHCO/HCO-free medium, cells were switched back to the
Cl-containing solution. This resulted in rapid cell
acidification back to baseline due to activation of the
Cl/HCO/HCO36Cl influx.
CFPAC-WT and CFPAC-1 cells were grown in collagen-coated 30-mm
Millicell-HA culture dish inserts (0.45 µM porosity) for 10-12 days (10) and assayed for DIDS-sensitive and -insensitive
36Cl uptake from the lower (basolateral
surface) or upper compartment (apical surface). The integrity of the
confluent cell monolayer was assessed by a lack of significant
transport of 36Cl from the upper compartment
to the lower compartment under control conditions (<0.1% of the
36Cl appeared in the lower compartment after
5 min). The culture medium was aspirated, and both surfaces were washed
in a solution consisting of 140 mM chloride salt of
N-methyl-D-glucamine (NMDG), pH 7.4. For uptake
experiments across the lower compartment (basolateral surface), 500 µM DIDS and 200 µM glybenclamide were added to the solution in the
upper compartment to inhibit apical AE and Cl channels,
respectively. For uptake experiments across the upper compartment
(apical surface), 500 µM DIDS and 200 µM glybenclamide were added
to the solution in the lower compartment to inhibit basolateral AE and
K+ channels, respectively. In separate studies, we
determined that 200 µM glybenclamide alone did not inhibit
Cl/base exchange activity (as measured with the
pH-sensitive dye BCECF) in cultured pancreatic duct (CFPAC-WT) cells
grown on coverslips. Interestingly, at 1 mM concentration,
glybenclamide inhibited Cl/HCO
salt of TMA and 130 mM NMDG gluconate,
pH 7.4. The reaction was terminated at 4 min using cold saline. The
experiments were performed in the presence or absence of 500 µM DIDS.
For uptake experiments across the apical surface, 0.5 mM DIDS was added
to the lower compartment to inhibit the basolateral AE. The uptake
experiments across the apical surface were performed in a manner
similar to those for the basolateral surface.
RNA isolation and Northern blot hybridization.
Total cellular RNA was extracted from CFPAC-1 and CFPAC-WT cells
according to the established methods (9), quantitated spectrophotometrically, and stored at 
80°C. Total RNA samples (30 µg/lane) were fractionated on a 1.2% agarose-formaldehyde gel,
transferred to Magna NT nylon membranes, cross-linked by ultraviolet
light, and baked. Hybridization was performed according to Church and
Gilbert (10), using [32P]dCTP (NEN, Boston,
MA)-labeled cDNA probes. The membranes were washed, blotted dry, and
exposed to a PhosphorImager screen (Molecular Dynamics, Sunnyvale, CA).
A 400-bp cDNA from the mouse DRA cDNA (EcoRI-EcoRI fragment) and a 1.8-kb cDNA from
human DRA cDNA [expressed sequence tag (EST) GenBank accession no.
AI805046, nt 1058-2858] were used for DRA Northern hybridizations
(the mouse probe has >95% homology to the human DRA and identifies an
identical band). For PDS, the full-length human cDNA obtained from a
thyroid cDNA library was used as a probe (37). For the
human PAT1 probe, a 2.5-kb RT-PCR product was obtained from human
CFPAC-1 cells using sense and antisense primers with the following
sequences: 5'-ATG CCT TCA CTG TGT CTC TCT GGT CTT GCC and 5'-AAT ATG
CAC CAG TTC CCT CCC TGT ACC GC. This fragment encodes nt 175 to 2699. For mouse PAT1, a 200-bp fragment was amplified by RT-PCR from a mouse
EST (GenBank accession no. AI747461) using the sense and antisense
oligonucleotide primers 5'-GGG AGA TTG AAG TGG AAG TGT ACA TC and
5'-AAG GCC AGA CTG ACT GCA ATA C. This PCR product corresponds to the
mouse sequence nt 2278 to 2468. A ~650-bp cDNA (SacI-Bgl2 fragment, nt 731-1379) from AE-1
cDNA, a ~1.6-kb fragment (codons 456-1002) from AE-2 cDNA, and a
~600-bp cDNA (SmaI-SmaI fragment, nt
28-625) from AE-3 cDNA of rat were used as specific probes. For
quantitation of Northern hybridization results, analysis of
hybridzation intensities was performed with ImageQuant software, using
grid volume measurement and background subtraction by grid-perimeter pixel averaging. Image volumes were normalized by dividing each grid
cell volume (DRA, PDS, PAT1, or 28S band intensity) by the mean grid
cell volume (band intensity) from an individual blot. Normalized grid
cell volumes were then divided by the normalized 28S rRNA for the same
gel lane to give DRA (or PAT1) mRNA-to-28S rRNA ratio for that sample.
Immunocytochemistry of DRA in mouse pancreas. Pancreas from normal mice was cut into slices and mounted on holders to form tissue blocks. The tissues were fixed in a solution containing 0.1% glutaraldehyde plus 2% paraformaldehyde in 0.1 M sodium cacodylate buffer, pH 7.2, and stored in 0.1 M cacodylate buffer, pH 7.2 at 4 °C. For immunohistochemistry, the tissue blocks were sectioned into 5-µm sections, placed on slides (Fisher Superfrost/Plus), and incubated at 75°C in the oven for 1 h. The slides were placed in 1% ZnSO4 in distilled H2O and heated in a microwave twice for 5 min, then cooled at room temperature for 15 min, and washed in distilled H2O twice for 3 min and in PBS twice for 3 min. To block the nonspecific binding, the slides were blotted, treated with a normal rabbit serum in a dilution of 1:10 in PBS plus 1% BSA, and incubated in a humidified chamber for 30 min at room temperature. A DRA-specific antibody (26) was applied to the slides in 1:100 dilution in PBS plus 1% BSA and the presence of saponin and incubated in a humidified chamber for 2 h at room temperature. The specificity of the DRA antibody has been demonstrated in colonocytes (26). The slides were washed three times in 200 ml PBS supplemented with horse serum at 6, 4, and 2 ml for 5, 5, and 10 min, respectively, at room temperature. The secondary antibody was applied to the slides in a dilution of 1:25. Each slide was treated in 4 µl secondary antibody, 5 µl normal horse serum, and 91 µl PBS plus 1% BSA, incubated in a humidified chamber for 1 h at room temperature, and then washed in PBS three times for 2 min each. The peroxidase-anti-peroxidase conjugate diluted in 1:100 in PBS plus 1% BSA was applied to the slides. Thereafter, the slides were incubated in a humidified chamber for 1 h at room temperature and then washed in PBS three times for 2 min each. To develop a colored reaction product, diaminobenzidine was used. Finally, the tissues were counterstained with Harris hematoxylin and mounted onto the slide using Fluoromount-G and covered with cover glass.
PAT1 antibody generation and immunoblot analysis. Polyclonal antibodies were raised in two rabbits against mouse PAT1 using a synthetic peptide with amino acid sequence MDLRRRDYHMERPLLNQEHL. The preimmune and immune sera of the third bleed were purified by an IgG purification kit (Sigma) and used for immunoblot analysis. Microsomes from cultured CFPAC-1 and CFPAC-WT cells were prepared and resolved by SDS-PAGE (30 µg/lane) and transferred to nitrocellulose membrane. The membrane was blocked with 5% milk proteins and then incubated for 6 h with 40 µl of PAT1 immune serum diluted at 1:400. The secondary antibody was a donkey anti-rabbit IgG conjugated to horseradish peroxidase (Pierce Chemical, Rockford, IL). The site of antigen-antibody complexation on the nitrocellulose membranes was visualized using the chemiluminescence method (SuperSignal Substrate, Pierce) and captured on light-sensitive imaging film (Kodak).
Statistical analyses. Values are expressed as means ± SE. The significance of difference between mean values was examined using ANOVA. P < 0.05 was considered statistically significant.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Cl/HCO/HCO/HCO/HCO
|
/HCO/HCO influx across the luminal surface of
cultured duct cells grown on permeable support was measured. Cells were
grown to confluence in 30-mm Millicell-HA culture dish inserts for
10-12 days and assayed for radiolabeled influx studies as
described in MATERIALS AND METHODS. The experiments were
performed in the presence or absence of DIDS. As indicated in Fig.
1C, both DIDS-sensitive and -insensitive luminal
36Cl influx increased in cells transfected
with functional CFTR (P < 0.01 vs. CFPAC-1 cells for
both DIDS-sensitive and -insensitive components), indicating the
upregulation of apical AE by CFTR in cultured pancreatic duct cells. In
the presence of 100 mM unlabeled Cl in the luminal
compartment, the absolute 36Cl uptake (in counts/min)
decreased as expected due to competition with the unlabeled
Cl; however, the pattern of increase in DIDS-sensitive
and -insensitive 36Cl influx in CFAPAC-WT cells remained
similar to the low Cl uptake solution.
Contrary to the luminal surface, the DIDS-sensitive
36Cl influx across the basolateral surface
was decreased by 33% in cells transfected with functional CFTR
(P < 0.05 vs. CFPAC-1 cells), indicating the
downregulation of basolateral AE by CFTR in cultured pancreatic duct
cells. The DIDS-insensitive 36Cl influx across the
basolateral membrane remained unchanged in CFPAC-WT cells.
Functional CFTR induces expression of
Cl/HCO/base exchanger in CFPAC-WT cells, we examined the
expression of a number of AEs by Northern hybridization. AE1 and AE3
were not detected. Interestingly, the expression of the ubiquitous AE2
was actually decreased in cells expressing the functional CFTR (Fig.
2A), with the AE2 mRNA
decreasing by ~40% in CFPAC-WT cells (P < 0.05, n = 3). These results indicate that none of these AEs
are responsible for enhanced apical Cl/base exchanger.
|
Expression and localization of DRA in mouse pancreas.
To determine whether DRA is expressed in native pancreatic tissue,
poly(A)+ RNA from mouse pancreas (Clonetech) was used for
Northern hybridization. The results, shown in Fig.
3, demonstrate that the mouse pancreas expresses high levels of DRA mRNA.
|
|
Expression of pendrin and PAT1.
Recently (37), pendrin, which is highly homologous and
adjacent to DRA on chromosome 7 (11), was found to mediate
apical Cl/HCO
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The results of current experiments demonstrate that DRA is
expressed in mouse pancreas and localized to the apical domain of the
duct cells (Figs. 3 and 4). DRA expression was also detected in
cultured human pancreatic duct cells and found to be upregulated by
functional CFTR (Fig. 2). The upregulation of DRA was associated with
enhanced apical Cl/HCO/HCO
DRA protein, which has been shown (13, 14) to mediate
sulfate, oxalate, and Cl transport in Xenopus
oocytes, was recently shown (23) to be a
Cl/HCO/HCO/HCO
HCO/HCO/HCO
PAT1 was recently cloned based on homology to DRA and pendrin
(22). PAT1 maps to chromosome 3 and encodes a
738-amino-acid protein (22). Immunohistochemical studies
(22) localized PAT1 to the apical membranes of the
pancreatic duct cells. The functional identity of PAT1 remains unknown;
however, based on its homology to DRA and pendrin, it has been
suggested to be an apical Cl/HCO
Increased Cl/HCO/HCO/HCO/HCO
It should be mentioned that the apical
Cl/HCO/HCO/HCO/HCO/HCO
The mechanism of the upregulation of DRA or PAT1 by CFTR remains
speculative. CFTR is a cAMP-sensitive Cl channel, and its
activation can affect a number of parameters including intracellular
Cl, membrane potential, or cell pH. Any increase in the
mRNA expression of DRA or PAT1 should, however, result from signals
that permeate the cell nucleus. Whether changes in cytoplasmic
parameters (i.e., membrane potential or Cl concentration)
can be transmitted to the nucleus and affect the expression of DRA or
PAT1 remains to be determined. The present studies were performed using
an in vitro expression system. It remains to be determined whether
altered expression of Cl/HCO
Recent studies from our (31) laboratory indicated that
activation of CFTR in functional CFTR-bearing duct cells (CFPAC-WT cells), but not in cells expressing a mutant CFTR (CFPAC-1 cells), stimulated the electrogenic NBC via membrane depolarization resulting from Cl secretion (24). According to these
studies (31), NBC mediates the uptake of
HCO/HCO
In conclusion, the apical transporter DRA (and PAT1) is upregulated by
functional CFTR and increases the
Cl/HCO/HCO
| |
ACKNOWLEDGEMENTS |
|---|
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants RO1-DK-54430 and DK-52821, a Merit Review Grant from the Department of Veterans Affairs, and grants from the Cystic Fibrosis Foundation and Dialysis Clinic Incorporated.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: M. Soleimani, Division of Nephrology and Hypertension, Univ. of Cincinnati Medical Center, 231 Bethesda Ave., MSB 5502, Cincinnati, OH 45267-0585 (E-mail: Manoocher.Soleimani{at}uc.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 23 March 2001; accepted in final form 3 August 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Abduladze, N,
Lee I,
Newman D,
Hwang J,
Boorer K,
Pushkin A,
and
Kurtz I.
Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.
J Biol Chem
273:
17689-17695,
1998
2.
Alper, SA,
Rossmann H,
Wilhelm S,
Stuart-Tilley AK,
Shmukler BE,
and
Seidler U.
Expression of AE2 anion exchanger in mouse intestine.
Am J Physiol Gastrointest Liver Physiol
277:
G321-G332,
1999
3.
Amlal, H,
and
Soleimani M.
Functional upregulation of H+-ATPase by lethal acid stress in cultured inner medullary collecting duct cells.
Am J Physiol Cell Physiol
273:
C1194-C1205,
1997
4.
Amlal, H,
Wang Z,
Burnham CE,
and
Soleimani M.
Functional characterization of a cloned Na+:HCO
5.
Argent, BE,
and
Case RM.
Pancreatic ducts: cellular mechanism and control of HCO
6.
Burnham, CE,
Amlal H,
Wang Z,
Shull GE,
and
Soleimani M.
Cloning and functional expression of a human kidney Na+:HCO
7.
Case, RM,
and
Argent BE.
Pancreatic duct cell secretion. Control and mechanisms of transport.
In: The Pancreas: Biology, Pathobiology, and Disease (2nd ed.), edited by Go VLW,
DiMagno ER,
Gardner JD,
Lebenthal FP,
Reber HA,
and Scheele GA.. New York: Raven, 1993, p. 301-350.
8.
Choi, JY,
Muallem D,
Kiselyov K,
Lee MG,
Thomas PJ,
and
Muallem S.
Aberrant CFTR-dependent HCO
9.
Chomczynski, P,
and
Sacchi N.
Single-step method of RNA isolation by acid guanidinium thiocynate-phenol-chloroform extraction.
Anal Biochem
162:
156-159,
1987[ISI][Medline].
10.
Church, GM,
and
Gilbert W.
Genomic sequencing.
Proc Natl Acad Sci USA
81:
1991-1995,
1984
11.
Everett, LA,
Glaser B,
Beck JC,
Idol JR,
Buchs A,
Heyman M,
Adawi F,
Hazani E,
Nassir E,
Baxevanis AD,
Sheffield VC,
and
Green ED.
Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).
Nat Genet
17:
411-422,
1997[ISI][Medline].
12.
Freedman, SD,
Kern HF,
and
Scheele GA.
Acinar lumen pH regulates endocytosis, but not exocytosis, at the apical plasma membrane of pancreatic acinar cells.
Eur J Cell Biol
75:
153-162,
1998[ISI][Medline].
13.
Hastabacka, J,
de la Chapelle A,
Mahtani MM,
Clines G,
Reeve-Daly MP,
Daly M,
Hamilton BA,
Kusumi K,
Trivedi B,
Weaver A,
Coloma A,
Lovett M,
Buckler A,
Kaitila I,
and
Lander ES.
The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping.
Cell
78:
1073-1087,
1994[ISI][Medline].
14.
Hoglund, P,
Haila S, J,
Socha Tomaszewski L,
Saarialho-Kere U,
Karjalainen-Lindsberg ML,
Airola K,
Holmberg C,
de la Chapelle A,
and
Kere J.
Mutations of the down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea.
Nat Genet
14:
316-319,
1996[ISI][Medline].
15.
Ishiguro, H,
Naruse S,
Kitagawa M,
Suzuki A,
Yamamoto A,
Hayakawa T,
Case RM,
and
Steward MC.
CO2 permeability and bicarbonate transport in microperfused interlobular ducts isolated from guinea-pig pancreas.
J Physiol (Lond)
15:
305-15,
2000.
16.
Ishiguro, H,
Steward C,
Lindsay AG,
and
Case RM.
Accumulation of intracellular HCO
17.
Kopelman, H,
Corey M,
Gaskin K,
Durie P,
Weizman Z,
and
Forstner G.
Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid and secretory defect in the cystic fibrosis pancreas.
Gastroenterology
95:
349-355,
1988[ISI][Medline].
18.
Kopito, RR.
Molecular biology of the anion exchanger gene family.
Int Rev Cytol
123:
177-183,
1999.
19.
Lebenthal, E,
Lerner A,
and
Rolston DK.
The pancreas in cystic fibrosis.
In: The Pancreas: Biology, Pathobiology, and Disease (2nd ed.), edited by Go VLW,
DiMagno ER,
Gardner JD,
Lebenthal FP,
Reber HA,
and Scheele GA.. New York: Raven, 1993, p. 1041-1081.
20.
Lee, MG,
Choi JY,
Luo X,
Strickland E,
Thomas PJ,
and
Muallem S.
Cystic fibrosis transmembrane conductance regulator regulates luminal Cl/HCO
21.
Lee, MG,
Wigley WC,
Zeng W,
Noel LE,
Marino CR,
Thomas PJ,
and
Muallem S.
Regulation of Cl/HCO
22.
Lohi, H,
Kujala M,
Kerkela E,
Saarialho-Kero U,
Kesteila M,
and
Kere J.
Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger.
Genomics
70:
102-112,
2000[ISI][Medline].
23.
Melvin, JE,
Park K,
Richardson L,
Schultheis PJ,
and
Shull GE.
Mouse down-regulated in adenoma (DRA) is an intestinal Cl/HCO
24.
Novak, I,
and
Greger R.
Effect of bicarbonate on potassium conductance of isolated perfused rat pancreatic ducts.
Pflügers Arch
419:
76-83,
1991[ISI][Medline].
25.
Poulsen, JH,
Fischer H,
Illek B,
and
Machen TE.
Bicarbonate conductance and pH regulatory capability of cystic fibrosis transmembrane conductance regulator.
Proc Natl Acad Sci USA
91:
5340-5344,
1994
26.
Rajendran, VM,
Black J,
Ardito TA,
Sangen P,
Alper SL,
Schweinfest C,
Kashgarian M,
and
Binder HJ.
Regulation of DRA and AE1 in rat colon by dietary Na depletion.
Am J Physiol Gastrointest Liver Physiol
279:
G931-G942,
2000
27.
Rosenstein, BJ,
and
Zeitlin PL.
Cystic fibrosis.
Lancet
351:
277-282,
1998[ISI][Medline].
28.
Scheele, GA,
Fukuoka S,
Kern HF,
and
Freedman SD.
Pancreatic dysfunction in cystic fibrosis occurs as a result of impairments in luminal pH, apical trafficking of zymogen granule membranes, and solubilization of secretory enzymes.
Pancreas
12:
1-9,
1996[ISI][Medline].
29.
Schoumacher, R,
Ram J,
Iannuzzi MC,
Bradbury NA,
Wallace RW,
Hon CT,
Kelly DR,
Schmid SM,
Gelder FB,
Rado TA,
and
Frizzell RA.
A cystic fibrosis pancreatic adenocarcinoma cell line.
Proc Natl Acad Sci USA
87:
4012-4016,
1990
30.
Schweinfest, CW,
Henderson KW,
Suster S,
Kondoh N,
and
Papas TS.
Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas.
Proc Natl Acad Sci USA
90:
4166-4170,
1993
31.
Shumaker, H,
Amlal H,
Frizzell R,
Ulrich CD,
and
Soleimani M.
CFTR drives Na+-nHCO secretion in CF.
Am J Physiol Cell Physiol
276:
C16-C25,
1999
32.
Shumaker, H,
Frizzell R,
Ulrich CD,
and
Soleimani M.
CFTR does not carry bicarbonate in cultured pancreatic duct cells (Abstract).
Gasteroenterology
118:
A1161,
1999.
33.
Shumaker, H,
and
Soleimani M.
CFTR upregulates the expression of basolateral Na-K-2Cl cotransporter in cultured pancreatic duct cells.
Am J Physiol Cell Physiol
277:
C1100-C1110,
1999
34.
Silberg, DG,
Wang W,
Moseley RH,
and
Traber PG.
The down regulated in adenoma (dra) gene encodes an intestine-specific membrane sulfate transport protein.
J Biol Chem
270:
11897-11902,
1995
35.
Sohma, Y,
Gray MA,
Imai Y,
and
Argent BE.
A mathematical model of the pancreatic ductal epithelium.
J Membr Biol
154:
53-67,
1996[ISI][Medline].
36.
Soleimani, M,
and
Burhham CE.
Physiologic and molecular aspects of the Na+:HCO
37.
Soleimani, M,
Greeley T,
Petrovic S,
Wang Z,
Amlal H,
Kopp P,
and
Burnham CE.
Pendrin: an apical Cl/OH/HCO
38.
Soleimani, M,
Singh G,
Bizal GL,
Gullans SR,
and
McAteer JA.
Na+/H+ exchanger isoforms NHE-2 and NHE-1 in inner medullary collecting duct cells: expression, functional localization, and differential regulation.
J Biol Chem
269:
27973-27978,
1994
39.
Soleimani, M,
and
Ulrich C.
How cystic fibrosis affects pancreatic HCO
40.
Wheat, VJ,
Shumaker H,
Burnham C,
Shull GE,
Yankaskas JR,
and
Soleimani M.
Cystic fibrosis transmembrane conductance regulator induces the expression of DRA (down-regulated in adenoma) along with Cl/HCO
This article has been cited by other articles:
|
|
 |
|
  E. Dube, L. Hermo, P. T.K Chan, and D. G Cyr Alterations in Gene Expression in the Caput Epididymides of Nonobstructive Azoospermic Men Biol Reprod, February 1, 2008; 78(2): 342 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Nickell, N. K. Kleene, and S. J. Kleene Mechanisms of neuronal chloride accumulation in intact mouse olfactory epithelium J. Physiol., September 15, 2007; 583(3): 1005 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ishiguro, W. Namkung, A. Yamamoto, Z. Wang, R. T. Worrell, J. Xu, M. G. Lee, and M. Soleimani Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G447 - G455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lamprecht and U. Seidler The emerging role of PDZ adapter proteins for regulation of intestinal ion transport Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G766 - G777. [Abstract] [Full Text] [PDF]
|
|
|
|
