Accumulation of weak base in gastric mucosa provides evidence for an acidic storage compartment

1989 ◽  
Vol 257 (5) ◽  
pp. G836-G844
Author(s):  
E. B. Ekblad ◽  
D. G. Warnock ◽  
V. Licko
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Nonlinear Least Squares ◽  
Secretion Rate ◽  
Weak Base ◽  
Fluorescence Detector ◽  
Flow Through ◽  
Intracellular Storage ◽  
Mucosal Side ◽  
Washout Curves

Uptake and release of acridine orange (AO), a fluorescent weak base that accumulates in acidic spaces, were studied in perfused frog gastric mucosa. Tissue was mounted between two flow-through chambers and loaded with AO on the mucosal side. AO washout and acid secretion rate were monitored simultaneously by a flow-through fluorescence detector and a pH-stat, respectively. Data were displayed on a computer screen, stored, and analyzed. AO, in concentrations as high as 0.02 mM, does not affect the acid secretion rate. Nonlinear least-squares analysis of AO washout curves resolved two exponential components: a faster component associated mainly with AO washout from the chamber and a slower component reflecting primarily AO washout from the tissue. The slower exponential declines more slowly at higher concentrations and/or longer duration of AO loading, whereas the faster exponential is unaffected. AO washout is unaffected by the level of the steady-state acid secretion rate. Nitrite inhibits the acid secretion rate but does not affect the AO washout. When nitrite is removed, acid secretion rate and fluorescence (AO concentration in the mucosal medium) increase simultaneously and transiently. The net amount of AO released from the tissue is proportional to the net amount of acid released. Stimulation by secretagogue in basally secreting tissue causes synchronous transient increases in acid secretion rate and fluorescence. We conclude that accumulation of AO provides evidence for the existence of an intracellular storage pool of free protons within the transporting epithelium.

Expression of NKCC1 and NKCC2 in gastric mucosa and their possible role in acid secretion

2010 ◽  
Vol 34 (8) ◽  
pp. S2-S2
Author(s):  
Tuo Ji ◽  
Hong Xue ◽  
Zhangfeng Dou ◽  
Yue Zhang ◽  
Jinxia Zhu
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion

Dynamics of a metabolic system: what single-action agents reveal about acid secretion

1992 ◽  
Vol 262 (3) ◽  
pp. G581-G592 ◽  
Author(s):  
V. Licko ◽  
E. B. Ekblad
Keyword(s):  
Acid Secretion ◽  
Independent Set ◽  
Nonlinear Least Squares ◽  
Data Sets ◽  
Estimation Of Parameters ◽  
Experimental Conditions ◽  
Metabolic System ◽  
Single Action ◽  
Adequate Representation ◽  
Dynamic Time

A simple single-state nonlinear mathematical model of an open metabolic system is shown to be an adequate representation of acid secretion in frog gastric mucosa. The parameters of the elemental model were estimated from data, and subsystems of augmented models were established for histamine, a nonconservative stimulus acting via binding to receptors, and for two inhibitors of acid secretion. The latter included metiamide, a nonconservative histamine antagonist, which affects the formation of acid by competitive binding to the histamine receptors, and nitrite, a conservative inhibitor, which affects the rate of acid translocation. For parameter estimation, two data sets were analyzed by a nonlinear least-squares procedure: a dynamic (time dependent) set consisting of individual acid secretion rate curves and an integral (time independent) set consisting of the curves of acid secreted and suppressed above or below baseline, respectively, as functions of agent exposure. Because the model is instrumental in the estimation of parameters of subsystems that are not accessible through direct observation, it can serve as a research tool in the investigation of the mechanism of gastric acid secretion under a variety of experimental conditions.

Nitric oxide inhibits gastric acid secretion by increasing intraparietal cell levels of cGMP in isolated human gastric glands

2005 ◽  
Vol 289 (6) ◽  
pp. G1061-G1066 ◽  
Author(s):  
Anna Berg ◽  
Stefan Redéen ◽  
Magnus Grenegård ◽  
Ann-Charlott Ericson ◽  
Sven Erik Sjöstrand
Keyword(s):  
Nitric Oxide ◽  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Enzymatic Digestion ◽  
Human Gastric Mucosa ◽  
Gastric Glands ◽  
Oxyntic Mucosa ◽  
No Donor

We have previously identified cells containing the enzyme nitric oxide (NO) synthase (NOS) in the human gastric mucosa. Moreover, we have demonstrated that endogenous and exogenous NO has been shown to decrease histamine-stimulated acid secretion in isolated human gastric glands. The present investigation aimed to further determine whether this action of NO was mediated by the activation of guanylyl cyclase (GC) and subsequent production of cGMP. Isolated gastric glands were obtained after enzymatic digestion of biopsies taken from the oxyntic mucosa of healthy volunteers. Acid secretion was assessed by measuring [14C]aminopyrine accumulation, and the concentration of cGMP was determined by radioimmunoassay. In addition, immunohistochemistry was used to examine the localization of cGMP in mucosal preparations after stimulation with the NO donor S-nitroso- N-acetylpenicillamine (SNAP). SNAP (0.1 mM) was shown to decrease acid secretion stimulated by histamine (50 μM); this effect was accompanied by an increase in cGMP production, which was histologically localized to parietal cells. The membrane-permeable cGMP analog dibuturyl-cGMP (db-cGMP; 0.1–1 mM) dose dependently inhibited acid secretion. Additionally, the effect of SNAP was prevented by preincubating the glands with the GC inhibitor 4 H-8-bromo-1,2,4-oxadiazolo[3,4-d]benz[b][1,4]oxazin-1-one (10 μM). We therefore suggest that NO in the human gastric mucosa is of physiological importance in regulating acid secretion. Furthermore, the results show that NO-induced inhibition of gastric acid secretion is a cGMP-dependent mechanism in the parietal cell involving the activation of GC.

Effect of dimethyl sulfoxide applications on gastric secretory function

1982 ◽  
Vol 63 (3) ◽  
pp. 24-25
Author(s):  
S. G. Vaynshteyn ◽  
Yu. V. Afanasyeva ◽  
D. H. Maksudova ◽  
M. I. Pivikova
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Dimethyl Sulfoxide ◽  
Chronic Gastritis ◽  
Secretory Function ◽  
Normal Acid

The use of applications of dimethyl sulfoxide in patients with ulcerative disease and chronic gastritis leads to suppression of increased acid secretion, ambivalence with normal acid secretion and has no effect in patients with atrophy of the gastric mucosa. The normalizing effect of dimethyl sulfoxide (DMSO) applications in persons with acidic, decompensated ^ and subcompensated states of the stomach by stimulating the neutralizing function of the antral glands was established. The use of dimethyl sulfoxide as a transporter of various drugs in physiotherapy can be indicated in patients with HC1 hypersecretion in the interdigestive phase of ventricular secretion.

Conservative and nonconservative inhibitors of gastric acid secretion

1987 ◽  
Vol 253 (3) ◽  
pp. G359-G368 ◽  
Author(s):  
E. B. Ekblad ◽  
V. Licko
Keyword(s):  
Steady State ◽  
Acid Secretion ◽  
Initial Step ◽  
No Net Loss ◽  
Apparent Loss ◽  
H2 Antagonist ◽  
Flow Through ◽  
Ph Stat ◽  
High Concentrations ◽  
Continuous Presence

Inhibitors of the initial step (H2-antagonist) and of the final step (thiocyanate, SCN-; and nitrite, NO2-) were used to study the dynamics of acid secretion in isolated frog gastric mucosa. Tissues were mounted in flow-through chambers, and the acid secretion rate (SR) was recorded on a pH-stat microprocessor. Continuous presence of H2-antagonist decreases the SR to a lower steady state, and on removal the SR returns to basal SR, causing a net loss of acid, the nonconservative effect. The amount of lost acid is a unique function of exposure, thus, independent of the patterns (pulses or steps) of inhibition. In contrast, continuous presence of SCN- or NO2- (below 3 mM) results in an undershoot in SR with a return to basal SR, whereas at higher concentrations there is no return. Removal of these inhibitors causes an overshoot in SR with return to basal SR. The rebound acid is equal to acid suppressed by NO2- and low concentration of SCN-, resulting in no net loss of acid, the conservative effect, whereas at high concentrations of SCN- there is an apparent loss of acid. In maximally secreting tissue the overshoot of SR is not observed. However, the acid is not lost, merely delayed. In resting tissue NO2- also merely delays the exit of the acid produced in response to forskolin. The rebound acid is proposed to reside in a sequestered "acid" pool that is stable for at least 120 min. Results with NO2- and SCN- suggest an effect on a saturable exit enzyme, possibly the K+-H+-ATPase.

Suppression of gastric acid secretion by furosemide in isolated gastric mucosa of guinea pig

1980 ◽  
Vol 239 (6) ◽  
pp. G532-G535 ◽  
Author(s):  
A. Ayalon ◽  
A. Corcia ◽  
G. Klemperer ◽  
S. R. Caplan
Keyword(s):  
Guinea Pig ◽  
Acid Secretion ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Electrical Conductance ◽  
Short Circuit Current ◽  
Cl Transport ◽  
Consequent Reduction ◽  
Net Flux ◽  
Mucosal Side

The effect of furosemide on acid secretion and Cl- transport was studied in isolated fundic mucosa of the guinea pig. Furosemide (10(-3) M), applied to the serosal side produced an immediate effect on the short-circuit current (Isc), lowering it by 47 +/- 2%. Potential difference decreased by 29 +/- 3%, electrical conductance by 18 +/- 4%, acid secretion by 38 +/- 1%, and net flux of Cl- from serosal-to-mucosal side by 37%. Application of the drug to the mucosal side produced similar effects on acid secretion and on the electrical parameters. It is suggested that furosemide blocks the entrance of Cl-, by the Na+--Cl- cotransport mechanism, through the basolateral membrane of the secreting cell. The consequent reduction in electrogenic Cl- transport would cause Isc and acid secretion to decrease. A reduction of Cl- conductance of the apical membrane, upon mucosal application of the drug, would cause similar effects on acid secretion and Cl- transport.

Intracellular pH measurements in gastric mucosa.

1979 ◽  
Vol 237 (1) ◽  
pp. E82
Author(s):  
S J Hersey
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Intracellular Ph ◽  
Ph Indicator ◽  
Active Secretion ◽  
Ph Measurements ◽  
Tubular Cells ◽  
A Value ◽  
Indicator Dye ◽  
Secretion Rates

Intracellular pH was measured in bullfrog gastric mucosa using a pH-indicator dye, bromthymol blue (BTB), with a spectrophotometric technique. Studies showed that BTB is taken up by the gastric mucosa and bound to intracellular components. The binding of BTB was shown to cause a shift in the pKa of the dye from the solution value of 6.95 to a value of 8.0. During the nonsecreting state, intracellular pH was estimated to be 7.4 (metiamide inhibition) or 7.1 (SCN inhibition). During active secretion of acid, intracellular pH increased with increasing secretion rates, reaching values in excess of pH 8. Using preparations from which the surface epithelial cells had been removed, it was shown that at least a portion of the alkaline response to stimulation occurs in the oxyntic or tubular cells. The results are interpreted in view of existing models for the chemical reaction involved in gastric acid secretion.

scholarly journals Effects of Cyclic Adenosine 3':5'-Monophosphate and Related Agents on Acid Secretion by Isolated Rabbit Gastric Mucosa

1975 ◽  
Vol 69 (2) ◽  
pp. 453-462 ◽  
Author(s):  
David Fromm ◽  
John H. Schwartz ◽  
Reynaldo Quijano
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion
Sign in / Sign up

Export Citation Format

Share Document