Indiana University School of Medicine, Department of Cellular and Integrative Physiology, Indianapolis, Indiana 46202
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ABSTRACT |
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Gastric secretion of hydrochloric acid requires protons and chloride, yet the mechanisms and regulation of gastric chloride secretion remain unclear. We developed an in vivo technique to simultaneously measure acid/base and chloride secretion into the gastric lumen of anesthetized rats. The cannulated stomach lumen was perfused with weakly pH-buffered chloride-free solution containing a chloride-sensitive fluorophore [5 µM N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE)]. Gastric acid and chloride secretion was detected in gastric effluents by 1) flow-through pH electrode and 2) MQAE fluorescence. Gastric effluent was also collected at 1-min intervals for independent determination of chloride amount by chloridometer. In all conditions, both optical and chemical determinations of chloride report similar amounts of secreted chloride. During luminal perfusion with pH 5 solution, net acid and chloride secretion into the lumen was observed. Pentagastrin stimulated both secretions. In contrast, proton pump inhibition (omeprazole) caused alkalinization of the gastric effluent, but chloride secretion was not diminished. During luminal pH 3 perfusion, net alkali secretion was observed, and chloride secretion at luminal pH 3 was greater than pH 5. When tissue is pretreated with omeprazole at luminal pH 3, the addition of prostaglandin E2 synchronously stimulates both alkali and chloride secretion. Results suggest that both acid and alkali secretions are separately coupled with chloride secretion.
proton pump, fluorescence, rat, stomach gastric luminal pH
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INTRODUCTION |
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IT WAS FIRST DEMONSTRATED almost 200 years ago that the stomach secreted hydrochloric acid (23). In the first half of the 20th century, many investigators explored chloride secretion as a means to understand mechanisms of hydrochloric acid formation (3, 8, 16, 23, 24, 33).
These early experiments identified three separable routes for chloride
secretion: an active transport component, an ion-exchange component,
and a passive ionic diffusion component (10, 13, 22, 33).
Active transport of chloride requires cellular metabolism and is
correlated with acid secretory rates (12, 22, 33). There
is also a Cl-dependent exchange reaction, defined as the
chloride secretory component stimulated by the presence of luminal
Cl
(13, 17, 21). Finally, passive
electrodiffusion of Cl
is driven by the transepithelial
potential according to the flux ratio equation (13). In
some cases, Cl
transport was more simply separated
into "acidic chloride transport" (coupled to gastric acid
secretion) and "nonacidic chloride transport" (19, 32,
35).
These early investigations defined most of our knowledge about gastric
chloride secretion but are derived solely from in vivo installation
(steady state) experiments (14, 15, 25, 27, 38) or in
vitro preparations of isolated amphibian mucosa (9-11, 13,
17-19, 22, 29, 32, 35). More recent information from mammalian systems has identified basolateral
Na+-K+-Cl cotransporter NKCC1 and
Cl
/HCO
channel that may represent an apical efflux route for
Cl
secretion in parietal cells (6, 28, 31,
36). Even with these more recent advances, we remain limited in
our knowledge about mechanisms and regulation of mammalian gastric
chloride secretion. In particular, we are aware of no studies that
explore whether gastric chloride secretion is coordinated with gastric bicarbonate secretion. Such questions are best answered by evaluating the dynamic regulation of mammalian chloride secretion.
Here, we report on-line quantitative measurements of chloride secretion from the rat stomach in vivo. Results build on our prior development of a method for simultaneous measurement of gastric effluents via pH electrode and fluorescent indicators. We show that gastric chloride secretion is increased in synchrony with both acid and alkali secretion. Results suggest that understanding the regulation and transport mechanisms of chloride secretion may provide a new window for understanding gastric physiology.
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METHODS |
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Animals. Male Sprague-Dawley rats (Harlan) were housed individually in cages with raised mesh floors to prevent coprophagia. Animals were deprived of food for 18-20 h before experimental use but had free access to water at all times. All experimental procedures were approved by the Animal Care and Use Committee of Indiana University.
Surgery. Animals were prepared for experiments as described previously (5). Briefly, 250-300 g rats were anesthetized with Inactin (100 mg/kg ip), and the right jugular vein was cannulated for intravenous administration of saline or drugs. The stomach was cannulated to permit continuous perfusion of the gastric lumen. The inlet tubing was routed through the esophagus and ligated at the cervical level. A CO2-impermeable tubing (Saran, Chicago; OD 3.28 × ID 1.79 mm) was ligated at the terminal pylorus and used to collect gastric effluent. Surgically prepared animals were allowed to stabilize 2-3 h before experimental use.
Gastric perfusion. The stomach lumen was perfused at 0.7 ml/min using a syringe pump (KDS 260, KD Scientific). In all experiments, stomach distension was avoided and results were not accepted if the stomach became distended during the experiment (e.g., due to perfusion blockage). Perfusates contained 150 mM NaNO3, 4 mM Homopipes, and 5 µM N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE; a chloride-sensitive fluorescent dye). In some experiments, NaCl replaced NaNO3. Before use, perfusates were titrated to either pH 5.0 or 3.0 with nitric acid (>69.5%, HNO3) or 10 N NaOH in chloride-free experiments and with 10 N HCl or 10 N NaOH in 150 mM NaCl experiments to approximate the physiological luminal pH measured in fed or fasted rat stomach, respectively (4). Gastric perfusion was run continuously except for defined periods in which perfusion was stopped transiently for 10 min. This "stop-flow" interval allowed intraluminal accumulation of gastric secretions (5) and thereby amplified observed changes. These enhanced changes of pH and chloride in perfusate were detected when perfusion was restarted and gastric contents left the stomach to flow past the downstream pH and chloride sensors. All measurements reported in the text were made at times when perfusion was running at 0.7 ml/min.
Gastric acid/base and chloride secretion. Gastric perfusion effluent was sequentially routed past an in-line reference and pH electrode (Microelectrodes, Bedford, NH) and then into a flow-through cuvette placed in a fluorometer (Fluorolog-3, JY Horiba/SPEX, Edison, NJ). A pH meter (Orion 720A, Orion Research, Beverly, MA) passed the pH-sensitive electrode signal to the host computer controlling the fluorometer. Data from both detectors were automatically and simultaneously recorded by the fluorometer host computer every 5 s. The pH electrode was calibrated by conventional pH standards flowed past the in-line electrode at the same rates as during experimental measurements.
Optical measurement of chloride was made using MQAE. Fluorescence emission at 450 ± 4 nm was measured by photon-counting photomultiplier tube in response to an excitation wavelength of 350 ± 1 nm. The fluorescence intensity was calibrated daily to solutions of known chloride concentrations. Chemical determination of chloride was made by chloridometer (Labconco, Kansas City, MO). Gastric effluent samples, after passing through the florometer cuvette, were collected at 1-min intervals for the 5 min before and 10 min after stop-flow. Chloride concentration of each time point was determined in triplicate using 200 µl gastric effluent added to 3 ml %10 perchloric acid (PCA). Results are presented as millimolar chloride. To stimulate gastric acid secretion in some experiments, pentagastrin was infused at 16 µg · kgChemicals. Drugs used were thiobutabarbital sodium salt (Inactin, RBI, Natick, MA), pentagastrin, and PGE2 (Sigma Chemical, St. Louis, MO), Homopipes (Research Organic, Cleveland, OH), MQAE (Molecular Probes, Eugene, Oregon), and omeprazole (a gift from J. D. Kaunitz, Los Angeles, CA). Pentagastrin and PGE2 were dissolved in absolute ethanol and then diluted with saline to a desired concentration (final EtOH <0.1%). Omeprazole was suspended at 28 mM in 0.5% (wt/vol) carboxymethycellulose and water. All agents were solubilized immediately before use. Routes of administration were intravenous infusion in a volume of 1 ml/h intraperitoneally in a volume of 0.5 ml/100 g body wt or intraluminally at a rate of 0.7 ml/min.
Statistics. Data are presented as the means ± SE from four to eight rats per group. Statistical comparisons between two groups used an unpaired two-tailed Student's t-test. Statistical comparisons between groups used one-way ANOVA followed by Dunnett's multiple-comparison test. P < 0.05 was considered significant.
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RESULTS |
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We perfused the stomachs of anesthetized rats with either pH 5 or 3 solution and measured pH of the gastric effluent to detect net gastric acid/base secretion. In a previous study, we demonstrated that luminal pH regulated the conversion from net acid (at luminal pH 5) to net alkaline secretion (at luminal pH 3) in the whole stomach (5). Perfusion solutions were weakly pH buffered (4 mM Homopipes, pKa = 4.32) and contained 5 µM of the chloride-sensitive fluorescent dye MQAE. We used lightly buffered solution to control pH excursions during perfusion.
MQAE is a chloride-sensitive flourescent dye, shown in a previous study
(39) to be insensitive to changes in
HCO
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We first compared the effect of chloride removal from the gastric lumen
on gastric acid and alkali secretion. We examined two conditions where
either acid secretion predominated (luminal pH 5) or bicarbonate
secretion predominated (luminal pH 3) (5). As seen in Fig.
2, substitution of nitrate for chloride
did not have any effect on the net basal acid/alkali secretion detected during steady-state perfusion at either luminal pH 5 and 3. There was
also no difference after a stop-flow period had amplified the amount of
secreted acid or base in the perfusate. Results suggested that removal
of luminal chloride does not alter the balance between basal gastric
acid and bicarbonate secretion in rat. Therefore, subsequent
experiments measured gastric chloride secretion using a luminal
environment without added chloride in the presence of NO3.
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By flowing gastric effluent containing MQAE past a pH electrode and
then into a fluorometer cuvette, both pH and chloride concentration of
the effluent could be measured on-line. After calibration of both
signals to milliequivalents per liter of gastric effluent, it was
possible to directly compare the chloride ions and protons added by
gastric secretions. Figure 3 shows a
representative experiment with luminal pH 5 perfusion. During
continuous perfusion, pH was below that of the fresh perfusate,
demonstrating net acid secretion (5). A net secretion of
chloride was also observed into the chloride-free perfusate. After the
addition of pentagastrin (16 µg · kg1 · h
1 iv
infusion), similar increases in proton and chloride concentration were
observed, although chloride concentration was always higher than proton
concentration (n = 7 experiments; data not shown). Blocking H+,K+-ATPase activity (omeprazole, 60 mg/kg ip) diminished proton and chloride concentrations in
parallel. However, although proton secretion was completely abolished,
a significant amount of chloride continued to be reported in the lumen.
Results qualitatively confirm the presence of at least two components
of chloride secretion: one component coupled to proton secretion and a
second that is independent of proton secretion. These points are
confirmed in a more quantitative analysis in the following figures.
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Luminal pH 5.
Experiments were performed to quantify pH and chloride secretion
simultaneously during stimulated acid secretion. Results from the pH
measurement are shown in Fig.
4A. During continuous superfusion, steady-state pH in gastric effluents was 4.74 ± 0.04 (P < 0.001 vs. fresh perfusion solution pH 5.02 ± 0.01, n = 7), and the peak pH after stop-flow was
3.63 ± 0.30 (P = 0.007 vs. basal pH). Both
results confirm the existence of net acid secretion in the basal
condition. As in Fig. 3, pentagastrin was then used to stimulate
gastric acid secretion at luminal pH 5. After 16 µg · kg1 · h
1 iv
pentagastrin, effluent pH reached a new steady-state level after 20 min
(3.76 ± 0.20; P = 0.0011 vs. basal steady-state
pH). The peak pH after stop-flow was 1.84 ± 0.11 (P < 0.001 vs. pentagastrin steady-state pH).
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Luminal pH 3. Results at luminal pH 5 showed the presence of chloride secretion even when gastric acid secretion was blocked by omeprazole. We therefore used an alternative way to limit acid secretion by switching to luminal pH 3. Previously, Coskun et al. (5) showed that net alkaline secretion dominated over acid secretion at this luminal pH.
At luminal pH 3 (Fig. 6A), basal steady-state pH was 2.93 ± 0.02 (P = 0.03 compared with fresh perfusion solution pH 2.99 ± 0.01, n = 6). In contrast to this incorrectly low pH [as observed earlier (5)], net alkali accumulation was clearly observed after stop-flow, with the peak pH 3.24 ± 0.11 (P = 0.04 vs. steady-state pH). Subsequent omeprazole treatment blocked residual acid secretion, and steady-state pH was 3.02 ± 0.02 (P = 0.0003 vs. basal steady-state pH). After stop-flow, the gastric effluent accumulated substantial alkali, with the peak pH 3.66 ± 0.13 (P = 0.006 vs. omeprazole steady-state pH).
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DISCUSSION |
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Chloride ion is an important component of gastric secretion. Our goal was to introduce a method for measurement of gastric chloride secretion that complemented those applied previously. Earlier measurements of chloride isotopic flux or steady-state luminal accumulation had limited time resolution. Nonetheless, use of isotopic fluxes gave valuable information on some dynamic changes in chloride secretion and yielded high-fidelity measurements of transepithelial unidirectional fluxes (13, 17, 21). However, isotopic fluxes were difficult to apply in vivo, or even in vitro, to studies of mammalian stomach. Here, we introduce in vivo methods for the continuous and simultaneous measurement of chloride secretion and gastric pH in rats. During continuous perfusion in the baseline conditions at either pH 3 or 5, there was no significant difference between the steady-state chloride values reported by MQAE fluorescence vs. chloride titrator (P = 0.13 or 0.10, respectively), although the titrator values tended to be lower. A quantitative comparison of chloride transients between the fluorescence and chemical methods was not possible, because physically different samples were analyzed: fluorometric measurements are made every 5 s within the flow stream of the gastric effluent, whereas gastric effluent must be collected in a test tube for 1 min to provide adequate sample for subsequent titrator measurements. The optical method has excellent time resolution, and our experiments confirm that MQAE fluorescence, at least qualitatively, mirrors results from more conventional chemical determination of chloride.
A notable limitation of the new method is that it requires use of a
chloride-free luminal perfusate. In the classic nomenclature of Forte
(13), this experimental condition eliminates the
Cl-exchange diffusion or the component of
Cl
secretion that requires luminal Cl
. This
may not be a crucial limitation, because there is no known physiological significance of the Cl
exchange diffusion.
Furthermore, several of our results confirm previous reports from
amphibian preparations that numerous physiologically important
functions remain intact in the absence of the Cl
-exchange
diffusion. As reported in bullfrog stomach (10, 13), changing the luminal chloride compositions did not affect net acid
secretion from rat stomach. In the absence of luminal Cl
,
the bullfrog stomach still manifests at least two distinct routes for
Cl
secretion: the active component (sensitive to
anoxia, stimulated by acid secretion) and the ionic diffusion (driven
by transepithelial voltage). In rat, we observed that one component of
Cl
secretion was stimulated by the activation of acid
secretion (pentagastrin), in contrast to another that could actually be stimulated in the absence of acid secretion. In both rat and frog, addition of omeprazole blocks acid secretion but not Cl
secretion (35). We do not know whether the "nonacidic"
Cl
secretion is due to ionic diffusion, because we can
neither measure nor reliably manipulate transepithelial potential in
the in vivo preparation. However, our experiments can reliably report
the effect of physiological or pharmacological manipulation of gastric acid/base status on overall Cl
secretion.
The nonacidic Cl secretion had properties that strongly
suggested its magnitude was correlated with the magnitude of
bicarbonate secretion. Omeprazole unmasks bicarbonate secretion without
affecting accompanying chloride secretion. In the presence of
omeprazole, Coskun et al. (5) previously observed that
gastric bicarbonate secretion was greater at luminal pH 3 compared with
luminal pH 5. In the current report, we observed that Cl
secretion was also greater at luminal pH 3 compared with luminal pH 5 (compare Figs. 5 and 6). At a minimum, this implies that some component
of Cl
secretion is controlled by luminal pH. This could
be a direct effect of extracellular protons on an apical ClC-2
Cl
channel, known to cause channel opening with a
pKa of ~5 (6, 36). It is also consistent
with activation of the ClC-2 channel through the direct effect of
omeprazole or changes in membrane potential (7) or
recruitment of alternative chloride secretory mechanisms in diverse
cell types of the stomach. Alternatively, it could be because the
nonacidic Cl
secretion is a facet of bicarbonate
secretion. The ability of PGE2 to elicit synchronous
undulations in bicarbonate and Cl
secretion (Fig. 7)
supports this last possibility.
At a minimum, it seems unlikely that an apical
Cl/HCO
(Fig. 2) and the surge in
Cl
secretion that occurs following stimulation of
bicarbonate secretion with PGE2 in the acid-supressed
stomach. In analogy to duodenal models, it may be that the activation
of an apical anion conductance (ClC-2?) serves as a route for both
bicarbonate and chloride exit into the lumen (20, 26).
In summary, we have developed and applied a new in vivo method for
measurement of gastric Cl secretion. Results reveal a
connection between the mechanisms that either mediate or regulate
gastric bicarbonate and Cl
secretion. It is hoped that
further research will be able to resolve the basis for the connection
and further develop our understanding of the nonacidic Cl
secretory mechanism.
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ACKNOWLEDGEMENTS |
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We acknowledge the pivotal role of S. Chu in the initial development of this technique.
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FOOTNOTES |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant RO1-DK-54940.
Address for reprint requests and other correspondence: M. H. Montrose, Indiana Univ. School of Medicine, Dept. of Cellular and Integrative Physiology, Med Sci 307, 635 Barnhill Dr., Indianapolis, IN 46202-5120 (E-mail: mmontros{at}iupui.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.
July 17, 2002;10.1152/ajpgi.00184.2002
Received 14 May 2002; accepted in final form 8 July 2002.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Allen, J,
Bishop A,
Daly M,
Larsson H,
Carlsson E,
Polak J,
and
Bloom S.
Effect of inhibition of acid secretion on the regulatory peptides in the rat stomach.
Gastroenterology
90:
970-977,
1986[ISI][Medline].
2.
Aurang, K,
Wang J,
and
Lloyd K.
Somatostatin inhibition of acid and histamine release by activation of somatostatin receptor subtype 2 receptors in rats.
J Pharmacol Exp Ther
281:
245-252,
1997
3.
Berglund, H,
Johnson R,
and
Chang HC.
The relationship between hydrochloric acid and total chlorides in gastric juice and on the possibility of standards for gastric secretion.
Acta Med Scand
86:
269-291,
1935.
4.
Chu, S,
Tanaka S,
Kaunitz J,
and
Montrose M.
Dynamic regulation of gastric surface pH by luminal pH.
J Clin Invest
103:
605-612,
1999
5.
Coskun, T,
Chu S,
and
Montrose MH.
Intragastric pH regulates conversion from net acid to net alkaline secretion by the rat stomach.
Am J Physiol Gastrointest Liver Physiol
281:
G870-G877,
2001
6.
Cuppoletti, J,
Baker AM,
and
Malinowska DH.
Cl channels of the gastric parietal cell are active at low pH.
Am J Physiol Cell Physiol
264:
C1609-C1618,
1993
7.
Cuppoletti, J,
Tewari K,
Sherry A,
Kupert E,
and
Malinowska D.
CIC-2 Cl channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole.
Am J Physiol Cell Physiol
281:
C46-C54,
2001
8.
Davenport, HW,
and
Fisher R.
The mechanism of the secretion of acid by the gastric mucosa.
Am J Physiol
131:
165-175,
1940
9.
Durbin, RP.
Anion requirements for gastric acid secretion.
J Gen Physiol
47:
735-748,
1964
10.
Durbin, RP.
Chloride transport and acid secretion in stomach.
Gastroenterology
73:
927-930,
1977[ISI][Medline].
11.
Forte, J,
Adams P,
and
Davies R.
Source of gastric mucosal potential difference.
Nature
197:
874-876,
1963[ISI].
12.
Forte, JG.
The effect of inhibitors of HCl secretion on the unidirectional fluxes of chloride across bullfrog mucosa.
Biochim Biophys Acta
150:
136-145,
1968[ISI][Medline].
13.
Forte, JG.
Three components of Cl flux across isolated bullfrog gastric mucosa.
Am J Physiol
216:
167-174,
1969
14.
Gardham, J,
and
Hobsley M.
The electrolytes of alkaline human gastric juice.
Clin Sci (Colch)
39:
77-87,
1970[ISI][Medline].
15.
Gray, J,
and
Bucher G.
The composition of gastric juice as a function of the rate of secretion.
Am J Physiol
133:
542-550,
1941
16.
Gray, JS.
The physiology of the parietal cell with special reference to the formation of acid.
Gastroenterology
1:
390-400,
1943.
17.
Heinz, E,
and
Durbin RP.
Studies of the chloride transport in the gastric mucosa of the frog.
J Gen Physiol
41:
101-117,
1957
18.
Hersey, A,
and
Sachs G.
Gastric acid secretion.
Physiol Rev
75:
155-189,
1995
19.
Hersey, S.
Acid secretion by frog gastric mucosa is electroneutral.
Am J Physiol Gastrointest Liver Physiol
248:
G246-G250,
1985
20.
Hogan, D,
Crombie D,
Isenberg J,
Svendsen P,
Schaffalitzky de Muckadell OB,
and
Ainsworth M.
CFTR mediates cAMP and Ca2+-activated duodenal epithelial HCO
21.
Hogben, CAM
Active transport of chloride by isolated frog gastric epithelium origin of the gastric mucosal potential.
Am J Physiol
180:
641-649,
1955[ISI].
22.
Hogben, CAM
The chloride transport system of the gastric mucosa.
Proc Natl Acad Sci USA
37:
393-395,
1951[ISI][Medline].
23.
Hollander, F.
The chemistry and mechanics of hydrochloric acid formation in the stomach.
Gastroenterology
1:
401-430,
1943.
24.
Hollander, F.
Studies in gastric secretion. II. A comparison of criteria of acidity used in this investigation.
J Biol Chem
91:
481-492,
1931
25.
Hollander, F.
Studies in gastric secretion. IV. Variations in the chlorine content of gastric juice and their significance.
J Biol Chem
97:
585-604,
1932
26.
Illek, B,
Fischer H,
and
Machen T.
Genetic disorders of membrane transport. II. Regulation of CFTR by small molecules including HCO
27.
Lindner, A,
Cohen N,
Dreiling D,
and
Janowitz H.
Electrolyte changes in the stomach following instillation of acid solutions.
Clin Sci (Colch)
25:
195-205,
1963[ISI].
28.
Malinowska, DH,
Kupert EY,
Bahinski A,
Sherry AM,
and
Cuppoletti J.
Cloning, functional expression, and characterization of a PKA-activated gastric Cl channel.
Am J Physiol Cell Physiol
268:
C191-C200,
1995
29.
Manning, EC,
and
Machen TE.
Effects of bicarbonate and pH on chloride transport by gastric mucosa.
Am J Physiol Gastrointest Liver Physiol
243:
G60-G68,
1982
30.
McDaniel, N,
and
Lytle C.
Parietal cells express high levels of Na-K-2Cl cotransporter on migrating into the gastric gland neck.
Am J Physiol Gastrointest Liver Physiol
276:
G1273-G1278,
1999
31.
Reenstra, W,
and
Forte J.
Characterization of K+ and Cl conductances in apical membrane vesicles from stimulated rabbit oxyntic cells.
Am J Physiol Gastrointest Liver Physiol
259:
G850-G858,
1990
32.
Reenstra, WW,
Bettencourt JD,
and
Forte JG.
Mechanisms of active Cl secretion by frog gastric mucosa.
Am J Physiol Gastrointest Liver Physiol
252:
G543-G547,
1987
33.
Rehm, WS.
A theory of the formation of HCl by the stomach.
Gastroenterology
14:
401-417,
1950[ISI].
34.
Rossmann, H,
Bachmann O,
Wang Z,
Schull G,
Obermaier B,
Stuart-Tilley A,
Alper S,
and
Seidler U.
Differential expression and regulation of AE2 anion exchanger in rabbit parietal and mucous cells.
J Physiol
534:
837-848,
2001
35.
Starlinger, M,
Hollands M,
Rowe P,
Matthews J,
and
Silen W.
Chloride transport of frog gastric fundus: effects of omeprazole.
Am J Physiol Gastrointest Liver Physiol
250:
G118-G126,
1986
36.
Stroffekova, K,
Kupert EY,
Malinowska DH,
and
Cuppoletti J.
Identification of the pH sensor and activation by chemical modification of the CIC-2G Cl channel.
Am J Physiol Cell Physiol
275:
C1113-C1123,
1998
37.
Takeuchi, K,
Ueshima K,
and
Okabe S.
Stimulation of gastric bicarbonate secretion by the analog of thyrotropin-releasing hormone, YM-14673, in the rat.
J Pharmacol Exp Ther
256:
1057-1062,
1991[Abstract].
38.
Teorell, T.
Electrolyte diffusion in relation to the acidity regulation of the gastric juice.
Gastroenterology
9:
425-443,
1947[ISI].
39.
Verkman, A,
Sellers M,
Chao A,
leung T,
and
Ketcham R.
Synthesis and characterization of improved chloride-sensitive fluorescent indicators for biological applications.
Anal Biochem
178:
355-361,
1989[ISI][Medline].