| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 II Department of Surgery, University of Helsinki, 00290 Helsinki; and 2 Chemical Technology, Technical Research Center of Finland, 33101 Tampere, Finland
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Luminal acid causes intracellular acidification in the gastric epithelium, but the mechanism by which H+ enters surface cells remains obscure. This study addressed the problem by assessing how different acids affect intracellular pH in gastric surface cells. Isolated Necturus maculosus antral mucosa was exposed to HCl, HNO3, H2SO4, and H3PO4 at pH 2.30. Intracellular pH was measured with microelectrodes. The physicochemical interaction of a synthetic model of gastric phospholipids with the different acids was studied using Langmuir film balance. Exposure to luminal HNO3, H2SO4, or H3PO4 caused significantly larger intracellular acidification than exposure to HCl. The degree of acidification was not dependent on the valence or nature of the anionic counterion of the acid but significantly correlated with the amount of molecular acid. By Langmuir film balance, subphases acidified with HNO3, H2SO4, or H3PO4 caused more close packing of phospholipid molecules than those acidified with HCl, possibly allowing hydrogen bonding between head groups to facilitate H+ movement across the phospholipid membrane. HCl causes significantly less intracellular acidification in gastric epithelium than HNO3, H2SO4, or H3PO4. This may be caused by the lower amount of molecular HCl in solution and possible hydrogen bonding between the head groups of phospholipid molecules and the other acids.
phospholipid membrane; hydrogen ion; microelectrodes
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THE GASTRIC MUCOSA IS
CONTINUOUSLY exposed to relatively strong luminal acid, which
implies that there are effective mechanisms to protect the mucosa
against acid-induced damage and to maintain intracellular pH
(pHi) within the physiological range in the surface epithelial cells. Direct measurements with microelectrodes in isolated
Necturus maculosus antral mucosa indicate that exposure of
the mucosa to physiological intragastric concentrations of HCl lowers
pHi slightly but significantly in surface epithelial cells
(10, 11), thus implying that some luminal H+
does penetrate inside the cells. These studies also showed that the
surface cells are much more resistant against exposure to luminal acid
than basolateral acid (10). One obvious reason for this
disparity is the preepithelial mucus-HCO
The apical membrane of gastric surface epithelial cells, like other cell membranes in eukaryotic cells, is composed of a phospholipid bilayer that, in principle, is virtually impermeable to electrically charged ions such as H+ (1). A cation (Na+) transport channel has been identified in the apical cell membrane of gastric surface epithelial cells (15). However, in the presence of luminal acid, these channels are blocked (17), thus precluding major transport of luminal H+ inside the cell via these channels.
Gutknecht and Walter (8) proposed that the entry of
luminal H+ inside the gastric mucosa might occur in the
form of molecular HCl. Phospholipid bilayers are, in general, highly
permeable to small uncharged molecules (1), and direct
calculations suggest that at normal intragastric pH, sufficient amounts
of molecular HCl exist to account for "H+ back
diffusion" in this condition (2). Gutknecht and Walter (8) proposed that monovalent acids are more permeant in
phospholipid bilayers than divalent acids. On the other hand, Barreto
and Lichtenberger (2) showed that it is the anionic
counterion that dictates the permeation of H+ in
phospholipid bilayers, Cl
permitting much higher
H+ permeation than SO
In the present study, we investigated acid movement across the apical cell membrane of surface epithelial cells in isolated Necturus antral mucosa by exposing the mucosa to various inorganic acids with different valences and anionic counterions and by comparing their effects on pHi with that of HCl. Moreover, to explore the potential interaction of different acids with phospholipid membrane, a synthetic model of human gastric mucosal phospholipids was spread onto the air-water interface to form a monomolecular Langmuir film, which was used as a simple model system for studying the influence of the acids on the monolayer. According to calculated size and water-to-octanol partition ratios of HCl, HNO3, H3PO4, and H2SO4, HCl should have the fastest diffusion rate through the plasma membrane.
| |
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The experimental setup and microelectrode technique were described in more detail previously (10). Necturi (Necturus maculosus) were obtained from St. Croix Biological supplies (Stillwater, MN) and kept in filtered water at 15-18°C. Animals were anesthetized by immersion in 1% tricaine methanesulfonate. The antral portion of the stomach was resected, stripped of its seromuscular coat, and mounted mucosal side up in a perfusion chamber. The mucosal (volume 0.15 ml) and serosal (volume 0.15 ml) half-chambers were perfused individually at room temperature at a rate of 1.5 ml/min, keeping the pressure at the serosal side slightly negative to hold the tissue steadily against its wire mesh support. After the tissues were mounted, they were allowed to stabilize for 30-60 min before the experiment was started.
Solutions and Chemicals
The standard Ringer solution contained (in mM) 105 Na+, 2 Ca2+, 5 K+, 1 Mg2+, 93 Cl, 18 HCOMeasurement of pHi
pHi was measured with double-barreled proton-selective microelectrodes. In short, borosilicate tubing with fiber in both barrels (2 GC 150F; Clark Electromedical, Pangbourne, UK) was pulled into micropipettes with an outer tip diameter of <0.5 µm. The pH-selective barrel was silanized with N,N-dimethyltrimethylsilylamine (Fluka, Buchs, Switzerland) vapor at 140°C. The filling solution for the pH-selective barrel contained 150 mM NaCl and 200 mM HEPES at pH 7.5, and the liquid proton sensor was the Hydrogen Ion Ionophore II Cocktail A (Fluka). The electrodes were calibrated in a series of 10 mM Ringer-MES and Ringer-HEPES buffers before and after each experiment. The other barrel, filled with 0.6 M KCl and 0.8 M Na-acetate, was used for measurement of the apical transmembrane potential (Vcm). An Ag-AgCl reference electrode was connected to the mucosal half-chamber via an agar-KCl bridge.Under microscopic control and with a micromanipulator (Prior), a
surface epithelial cell was impaled by the double-barreled pH-sensitive
electrode. The experiment was not started until stable readings were
obtained for 10-15 min. The electrometer amplifier used with the
pH-selective microelectrode had an input leakage current of
<1014 A and input impedance of 
1014 
.
The signals of the pH-selective barrel (H+ activity + Vcm) and the voltage barrel
(Vcm) were subtracted to give the net
H+ activity signal.
Measurement of Electric Potentials and Resistances
The transepithelial potential (Vms) was measured with an Ag-AgCl electrode connected to the serosal half-chamber via an agar-KCl bridge with a similar mucosal half-chamber electrode as reference. For resistance measurements, current pulses of 15-30 µA/cm2 magnitude and 1-s duration at 30-s intervals were applied from a current pulse generator through the epithelium by means of two Ag-AgCl electrodes located in the mucosal and serosal half-chambers.Transepithelial resistance (Rt) was calculated
from Rt = 
Vms/I, where
Vms is the transepithelial voltage deflection
caused by the current pulse and I is the magnitude of a
current pulse. The ratio of apical and basolateral cell membrane
resistances (Ra/Rb, where
Ra is resistance of apical membrane and
Rb is resistance of basolateral membrane) was
calculated from the voltage deflections generated by the current pulse
across the apical (Vcm) and basolateral (Vcs) cell membranes
(Ra/Rb = Vcm/Vcs,
Vcs = Vms 
Vcm). The chamber resistance was
subtracted from the values for Vcm and
Vms.
Langmuir Film Balance
A KSV 2200 Langmuir trough (KSV Instruments) with a Pt-Wilhelmy balance was used for monolayer studies (13). A synthetic model of human gastric mucosal phospholipids was prepared with commercial phospholipids (Sigma). The composition of the phospholipid mixture was as follows: phosphatidylcholine 44.8%, phosphatidylethanolamine 31.5%, phosphatidylinositol 10.8%, sphingomyelin 6.9%, cardiolipin/unknown 4.1%, and lysophosphatidylcholine 1.9% (18). The phospholipid mixture was dissolved in chloroform at a concentration of 1 mg/ml and spread onto a water subphase. The water was purified with a Millipore Milli-Q filtering system. The solvent was allowed to evaporate for a sufficiently long time, after which the surface pressure-area isotherms were recorded by compressing the spread phospholipids at a speed of 10 mm/min with the aid of a barrier. During compression, the monolayer undergoes a number of phase transformations. The different phases resemble two-dimensional analogs of gases, liquids, and solids. Several recordings were made to ensure the reproducibility of the isotherms. The isotherms were recorded at room temperature (21°C), and pH was reduced from 5.6 (pH of unbuffered water) to 3.0, 2.3, or 1.5 with one of the following acids: HCl, HNO3, H2SO4, or H3PO4.Molecular Modeling
Van der Waals volumes and octanol-to-water partition ratios (complete neglect of differential overlap method was used to calculate partial charges) were estimated using Molecular Modeling pro (ChemSW, Fairfield, CA).Statistics
Results are given as means ± SE. Statistical analysis of the raw data was performed using Student's t-test for paired variates. Pearson's correlation coefficient R was used in correlation analysis.| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Effect of HCl
Intracellular pH.
pHi in mucosas exposed to luminal pH 6.0 was 7.24 ± 0.02. Luminal exposure to HCl (pH 2.3, pKa 7),
caused rapid intracellular acidification followed by a steady-state
pHi of 7.15 ± 0.03 (n = 11;
P < 0.001). During the recovery period after removal
of luminal acid (10 min), pHi returned to the previous
level (Fig. 1).
|
Resistances.
Exposure to luminal HCl (pH 2.3) did not change transmucosal resistance
(Rt) [from 766 ± 49 to 754 ± 80 · cm2; not significant (NS)]. At the same
time, Ra/Rb increased
significantly from 3.21 ± 0.63 to 6.19 ± 0.90 (P < 0.02) and returned to the previous level
(3.18 ± 0.34) after the change back to luminal pH 6.0 exposure.
Electric potentials.
Exposure to luminal HCl (pH 2.3) provoked a significant
hyperpolarization of apical membrane potential
(Va; from 33.3 ± 3.5 to 44.3 ± 4.0 mV; P < 0.01). During the following pH 6.0 exposure, it returned to 36.6 ± 3.1 mV.
Effect of HNO3
Intracellular pH.
pHi was 7.26 ± 0.02 in mucosae exposed to luminal pH
6.0 (n = 11). Exposure of the mucosae to
HNO3 (pH 2.3, pKa 1.3) caused a
rapid acidification of pHi to 7.08 ± 0.03 in 4.5 min
(n = 11; P < 0.01). After removal of
luminal acid (luminal pH 6.0 exposure), pHi recovered to
7.28 ± 0.05. Compared with HCl at pH 2.3, HNO3 at pH
2.3 caused a significantly (P < 0.05) larger
acidification of pHi, pHi being 0.09 ± 0.01 and 0.18 ± 0.04 pH units for HCl- and
HNO3-treated tissues, respectively (n = 11, Fig. 2).
|
Resistances.
Exposure to HNO3 (pH 2.3) induced no statistically
significant change in Rt (from 650 ± 65 to
690 ± 77 · cm2; NS) or in
Ra/Rb (from 4.00 ± 0.55 to 3.45 ± 0.48; NS).
Electric potentials.
HNO3 at pH 2.3 caused a significant hyperpolarization in
Va (from 37.2 ± 3.4 to 56.7 ± 5.3 mV; P < 0.01), which recovered to 45.8 ± 2.7 mV after removal of luminal acid. There were no significant
differences in the behavior of Rt,
Va, or
Ra/Rb during HCl and
HNO3 exposures in the same tissues.
Effect of H2SO4
Intracellular pH.
Acidification of the luminal perfusate to pH 2.3 with
H2SO4 (pKa 3) caused a
rapid decrease of pHi from 7.26 ± 0.02 to 7.09 ± 0.03 (n = 11; P < 0.01). When
tissues were exposed to luminal pH 6.0 again, pHi recovered
in 2 min to the baseline level (7.26 ± 0.04; Fig. 1).
H2SO4 caused a significantly larger
acidification than HCl, pHi being 0.09 ± 0.01 and
0.17 ± 0.04 pH units for HCl- and
H2SO4-treated tissues, respectively
(n = 11, Fig. 2).
Resistances.
Exposure to luminal H2SO4 (pH 2.3) did not
induce a change in Rt (from 772 ± 58 to
718 ± 60 · cm2; NS).
Ra/Rb increased
significantly (from 3.18 ± 0.34 to 7.34 ± 1.46;
P = 0.02) and recovered to 4.37 ± 0.48 after
return to luminal pH 6.0 exposure.
Electric potentials.
Exposure to H2SO4 (pH 2.3) induced a
significant hyperpolarization of Va (from
37.6 ± 3.4 to 44.8 ± 5.3 mV; P = 0.03),
which recovered to 33.7 ± 3.3 mV after return to luminal pH
6.0.
Effect of H3PO4
Intracellular pH.
Exposure of the mucosae to luminal H3PO4 at pH
2.3 (pKa 2.1) caused significant acidification
of pHi from 7.27 ± 0.05 to 7.03 ± 0.05 (n = 11, P < 0.01; Fig. 1). Compared
with the effects of HCl (pH 2.3) in the same tissues,
H3PO4 (pH 2.3) caused a statistically significantly larger acidification of pHi,
pHi being 0.09 ± 0.01 and 0.24 ± 0.05 pH
units for HCl and H3PO4, respectively,
(P < 0.05; Fig. 2). When changing back to luminal pH
6.0, the pH did not return to baseline level as with the other acids
but tended to decrease to a very low level (from 7.03 ± 0.05 to
6.74 ± 0.23, NS; Fig. 1).
Resistances.
Exposure to luminal H3PO4 (pH 2.3) decreased
Rt (from 712 ± 70 to 644 ± 54 · cm2; P < 0.01). After return
to luminal pH 6.0, Rt did not recover but stayed
at a low level (514 ± 42 · cm2).
Ra/Rb did not change
significantly (from 3.86 ± 0.67 to 6.57 ± 1.60;
P < 0.05).
Electric potentials.
Exposure to luminal H3PO4 (pH 2.3) did not
significantly change Va (from 45.9 ± 2.9 to 27.6 ± 4.2 mV; NS). The decrease in
Rt and direction of change in
Va were significantly different between HCl and
H3PO4 exposures in the same tissues, whereas
the changes in Ra/Rb were not.
substituted for phosphate), recovery of
pHi, Ra/Rb,
and Va was observed (data not shown).
Surface Pressure-Area Isotherms
Figure 3 demonstrates the surface pressure-area isotherms of gastric mucosal phospholipids formed on HCl subphases at pH 1.0, 1.5, and 2.3. There is only a minor difference in the isotherms, but the extrapolated mean molecular area (MMA) of the phospholipid mixture increased slightly with increase in pH. This was also observed on the other acidic subphases (Table 1 and Fig. 4). The increase in MMA was most drastic on subphases of HNO3, H2SO4, and H3PO4, with an increase between 11 and 28 Å2. The increase in MMA on the HCl subphase was only ~7 Å2. The phospholipids are more closely packed at pH 1.5 on all the acid subphases than on subphases with higher pH. The MMA on the HCl subphase was, moreover, much higher than that on the other acid subphases at pH 1.5, which showed no difference in MMA of the phospholipid mixture. There was no significant difference in collapse pressure (Table 1). The pKa values for each acid are given above in this section.
|
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The apical cell membrane of gastric surface epithelial cells, like other cell membranes in eukaryotic cells, is formed by a phospholipid bilayer, possibly uniquely covered by an additional hydrophobic phospholipid monolayer (9, 14). Phospholipid bilayers are highly impermeable to electrically charged ions but readily permeable to small uncharged molecules (1). The basal permeability of nonelectrolytes through the phospholipid bilayer is determined both by the octanol/water partition coefficient (which tells how easily the molecule enters the bilayer) and the diffusion coefficient of the molecule inside the membrane. For different nonelectrolytes the difference in the diffusion coefficient inside the same bilayer is mainly determined by the volume of the diffusing molecule, because the other factors (such as volume selectivity of the membrane and maximum diffusion speed) are independent of the diffusant (19). The estimated van der Waals volumes of the acids HCl, HNO3, H3PO4, and H2SO4 are 24, 43, 64, and 63 Å2, respectively. Different estimation methods of octanol-to-water partition ratios give slightly different values, but the order is always the same: HCl > HNO3 > H3PO4 > H2SO4. According to these results, the diffusion rate of HCl through the plasma membrane should theoretically be the fastest.
However, the cell membrane contains specific transport mechanisms, such
as ion channels, ion exchangers, and pumps, that also permit ion
movement across the phospholipid bilayer. An amiloride-sensitive Na+ channel (15) has been identified in the
apical membrane of gastric surface epithelial cells, and a
Cl-specific anion channel (16) and an
Cl/HCO3 exchanger
(7) have been postulated. The amiloride-sensitive Na+ channel is probably also permeant to protons, but these
channels are blocked in the presence of luminal acid (17).
It has been well documented that exposure of the gastric epithelium to acid leads to cytoplasmic acidification in surface epithelial cells (10). However, the mechanism by which H+ gets its access to the cell interior remains to be delineated. Earlier studies on proton diffusion across artificial phospholipid vesicle membranes indicated that the permeability of phospholipid bilayers to H+ is unexpectedly high, being much greater than the permeability to other small monovalent ions (4). Gutknecht and Walter (8) proposed on the basis of their investigations of proton and gastric acid transport across artificial planar lipid membranes that in the presence of large pH gradients proton transport occurs primarily as diffusion of the molecular form of HCl across the membrane. They also showed that the monovalent acid HNO3 expressed transport through membranes similar to that HCl, whereas the divalent acid H2SO4 showed no detectable H+ flux through artificial membranes (8).
To further investigate acid movement in gastric epithelium, we exposed
isolated Necturus antral mucosa to four inorganic acids with
different valence and molecular size, HCl, HNO3,
H2SO4, and H3PO4, at pH
2.3. All acids provoked rapid intracellular acidification but,
unexpectedly and deviating from the above studies, HCl caused less
intracellular acidification in gastric epithelium than
HNO3, H2SO4, or
H3PO4. The reason for this discrepancy remains
obscure, but our results are partially explicable in terms of the
relative amounts of molecular acid. In contrast to monobasic acids,
multibasic acids dissociate in several steps. Knowing the dissociation
constants it is possible to calculate the amount of the acid, which is
in the molecular form in an aqueous solution. At pH 2.3 in Ringer solution, the molecular concentrations for the acids used are as
follows: 49 pM HCl, 25 µM HNO3, 161 nM
H2SO4, and 39 mM H3PO4. Thus the molecular concentration of an acid (in logarithmic scale) in
aqueous solution seems to correlate with the degree of intracellular acidification provoked by it [Pearson's R = 0.48, P = 0.003, log(molecular concentration) vs.
pHi], which is in agreement with the concept that
gastric acid (like other acids) enters the surface cell, at least in
part, in an nonionized molecular form. The changes in osmolarity
between different acid solutions used are small (compared with HCl pH
2.3 solution: 25 µosmol/kgH2O, 2.2
mosmol/kgH2O, and 3.4 mosmol/kgH2O for
HNO3, H2SO4, and
H3PO4, respectively) and most probably do not
contribute to the results.
On the basis of studies with artificial phospholipid bilayer vesicles exposed to a high pH gradient Barreto and Lichtenberger (2) showed that the rate of intravesicular acidification is dependent on the nature of the anionic "counterion." Exposure of the vesicles to ambient HCl provoked a significantly larger intravesicular acidification than H2SO4 or H3PO4 with the same pH gradient (2). Our results are not in accordance with these findings, because intracellular acidification provoked by HCl was of lesser magnitude than that caused by H2SO4 or H3PO4. Further investigations with the vesicle model indicated that chloride is an important cofactor of acidification across artificial bilayers by forming a very membrane-permeant HCl molecule, and Barreto and Lichtenberger (3) proposed that this might be the mechanism for H+ back diffusion in the gastric mucosa.
The monolayer-forming properties of the synthetic model of human gastric mucosal phospholipids have been studied previously with the Langmuir film balance (pH 5.6 at room temperature and pH 2.1 at 37°C) (13). When different nonsteroidal anti-inflammatory drugs (in their aqueous solutions as sodium salts), which are weak acids, were used as a subphase, the MMA of the phospholipid mixture and their collapse pressure differed significantly (13).
In the present study the synthetic models of human mucosal phospholipids were spread onto an aqueous subphase acidified with HCl, HNO3, H2SO4, or H3PO4. There was a shift in MMA of the lipids depending on pH and acid. A clear distinction was observed at pH 1.5, where the phospholipids were more closely packed on subphases acidified with HNO3, H2SO4, or H3PO4 than at higher pH or on HCl subphases. The more compressed monolayers at low pH indicate a higher complexation between the phospholipid head group and the anion. Changes in the isotherm due to ionization will reflect on changes in the lateral attraction between the molecules and primary head group interactions. Apart from considering the degree of charge present, the specific nature of the head group must be taken into account. The phospholipid mixture was 31.5% phosphatidylethanolamine. Amine monolayers have been found to be more condensed on subphases containing divalent counterions such as sulfonate or hydrogen phosphate (5). Phosphatidylethanolamine, moreover, readily forms hydrogen bonds. The MMA of the dietary phospholipids at pH 5.6 was 84 Å2, which indicates that the phospholipids are getting more condensed as pH decreases (13). The MMA was higher on a subphase acidified with HCl than in those acidified with HNO3, H2SO4, or H3PO4 (pH < 3.0). Biegel and Gould (4) speculated that protons cross the phospholipid bilayer via a hydrogen-bond exchange mechanism along transmembrane H2O bridges, which, in turn, are formed by H2O molecules dissolved in the membrane hydrocarbon. Further studies demonstrated that such hydrogen-bonded chains of H2O molecules can provide substantial discrimination between protons and other monovalent cations, thus specifically allowing H+ permeation across the phospholipid membrane (6). In our experiments, the orientational order of the hydrocarbon chains was increased on subphases of HNO3, H2SO4, and H3PO4 and the head groups are probably close enough for hydrogen bonding to occur, thus permitting H+ to permeate the lipid layer through hydrogen bonds. This is in accordance with our observation that HCl causes less intracellular acidification in gastric epithelium than HNO3, H2SO4, and H3PO4, and the difference in the degree of acidification may also be explicable, at least in part, in terms of this mechanism.
| |
ACKNOWLEDGEMENTS |
|---|
This work was supported by grants from the Research Foundation of Helsinki University Central Hospital, Sigrid Juselius Foundation, and the Academy of Finland.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: E. Kivilaakso, Helsinki Univ. Central Hospital. II Dept. of Surgery, Haartmanninkatu 4, 00290 Helsinki, Finland (E-mail: eero.kivilaakso{at}hus.fi).
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 16 August 2000; accepted in final form 9 April 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Andersen, O.
Permeability Properties of Unmodified Lipid Bilayer Membranes. Membrane Transport in Biology. Berlin: Springer, 1978, p. 369-446.
2.
Barreto, J,
and
Lichtenberger L.
A phospholipid bilayer model for gastric membranes: vesicle acidification driven by a million fold proton gradient (Abstract).
Gastroenterology
98:
A19,
1990.
3.
Barreto, J,
and
Lichtenberger L.
Vesicle acidification driven by a millionfold proton gradient: a model for acid flux through gastric cell membranes.
Am J Physiol Gastrointest Liver Physiol
262:
G30-G34,
1992
4.
Biegel, CM,
and
Gould JM.
Kinetics of hydrogen ion diffusion across phospholipid vesicle membranes.
Biochemistry
20:
3474-3479,
1981[Medline].
5.
Binks, BP.
Insoluble monolayers of weakly ionizing low molar mass materials and their deposition to form dangmuir-Blodgett multilayers.
Adv Colloid Interface Sci
34:
343-432,
1991[Web of Science].
6.
Deamer, DW.
Proton permeation of lipid bilayers.
J Bioenerg Biomembr
19:
457-479,
1987[Web of Science][Medline].
7.
Flemström, G,
and
Garner A.
Gastroduodenal HCO
8.
Gutknecht, J,
and
Walter A.
Transport of protons and hydrochloric acid through lipid bilayer membranes.
Biochim Biophys Acta
641:
183-188,
1981[Medline].
9.
Hills, B,
Butler B,
and
Lichtenberger L.
Gastric mucosal barrier: hydrophobic lining to the lumen of the stomach.
Am J Physiol Gastrointest Liver Physiol
244:
G561-G568,
1983
10.
Kivilaakso, E,
and
Kiviluoto T.
Intracellular pH in isolated Necturus antral mucosa in simulated ulcerogenic conditions.
Gastroenterology
95:
1198-1205,
1988[Web of Science][Medline].
11.
Kiviluoto, T,
Mustonen H,
and
Kivilaakso E.
Effect of barrier-breaking agents on intracellular pH and epithelial membrane resistances: studies in isolated necturus antral mucosa exposed to luminal acid.
Gastroenterology
96:
1410-1418,
1989[Web of Science][Medline].
12.
Kiviluoto, T,
Ahonen M,
Bäck N,
Häppölä O,
Mustonen H,
Paimela H,
and
Kivilaakso E.
Preepithelial mucus-HCO
13.
Kivinen, A,
Vikholm I,
and
Tarpila S.
A film balance study of the monolayer-forming properties of dietary phospholipids and the interaction with NSAIDs on the monolayers.
Int J Pharm
108:
109-115,
1994.
14.
Lichtenberger, L,
Graziani L,
Dial E,
Butler B,
and
Hills B.
Role of surface-active phospholipids in gastric cytoprotection.
Science
219:
1327-1329,
1983
15.
Machen, TE,
Silen W,
and
Forte JG.
Na+ transport by mammalian stomach.
Am J Physiol Endocrinol Metab Gastrointest Physiol
234:
E228-E235,
1978
16.
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
17.
Mustonen, H,
and
Kivilaakso E.
Luminal acid increases apical cell membrane resistance in isolated necturus antral mucosa.
Gastroenterology
113:
875-883,
1997[Web of Science][Medline].
18.
Schmitz, M,
and
Renooj W.
Phospholipids from rat, human and canine gastric mucosa.
Gastroenterology
99:
1292-1296,
1990[Web of Science][Medline].
19.
Stein, W.
Transport and Diffusion Across Cell. San Diego: Academic, 1987.
This article has been cited by other articles:
|
|
 |
|
  O. Furukawa, M. Hirokawa, L. Zhang, T. Takeuchi, L. C. Bi, P. H. Guth, E. Engel, Y. Akiba, and J. D. Kaunitz Mechanism of augmented duodenal HCO3- secretion after elevation of luminal CO2 Am J Physiol Gastrointest Liver Physiol, March 1, 2005; 288(3): G557 - G563. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
c of human gastric
mucosal phospholipid monolayers formed on various acidic subphases
