Gastrin stimulation of isolated gastric glands

1982 ◽  
Vol 242 (5) ◽  
pp. G504-G512 ◽  
Author(s):  
C. S. Chew ◽  
S. J. Hersey
Keyword(s):  
Time Course ◽  
Gastric Gland ◽  
Cell Activity ◽  
Phosphodiesterase Inhibitor ◽  
Parietal Cells ◽  
Gastric Glands ◽  
Histamine H2 Receptor ◽  
Wide Range ◽  
Isolated Cell ◽  
Stimulation Of

The ability of gastrin to stimulate acid formation was studied in gastric glands and isolated parietal cells obtained from rabbit gastric mucosa. Accumulation of the weak base aminopyrine and increases in oxygen consumption were used as measures of acid secretory activity. The responses to gastrin were found to be very small (10-15% increase). However, inclusion of dithiothreitol (0.5 mM) in the incubation medium enhanced the responses in both glands and isolated cells to easily detectable levels. For the gastric gland preparation, gastrin stimulation was maximal at 1 X 10(-7) M, with an apparent ED50 of 5 nM. The response reached a maximum at about 30 min and was stable for at least an hour. The gastrin response was enhanced by the phosphodiesterase inhibitor isobutylmethylxanthine and partially inhibited by cimetidine, a histamine H2-receptor antagonist. Combinations of gastrin and histamine showed an additive response over a wide range of histamine concentrations. However, time-course studies revealed a transient potentiation of gastrin response by histamine, which reached a peak at 15 min and was reduced to an additive response by 30 min. Studies using isolated cell populations enriched in parietal cells (approximately 70%) revealed a gastrin stimulation that was not inhibited by cimetidine. The transient potentiation of the gastrin response by histamine was also found in the isolated cell preparation. Gastrin had no effect on cellular cAMP levels or adenylyl cyclase activity. The results are interpreted to indicate that gastrin stimulates acid secretion through three separate actions: 1) a direct stimulation of parietal cell activity, 2) a potentiating interaction with histamine, and 3) for more intact preparations, a release of histamine, which in turn acts as a paracrine stimulus. Quantitatively, the most important action appears to be the release of histamine. None of the actions of gastrin appear to involve a change in cAMP metabolism.

Intracellular Ca regulation during secretagogue stimulation of the parietal cell

1988 ◽  
Vol 254 (1) ◽  
pp. C130-C140 ◽  
Author(s):  
P. A. Negulescu ◽  
T. E. Machen
Keyword(s):  
Acid Secretion ◽  
Phosphodiesterase Inhibitor ◽  
Parietal Cells ◽  
Channel Blockers ◽  
Ca Channel ◽  
Gastric Glands ◽  
Intracellular Store ◽  
H2 Antagonist ◽  
Intracellular Ca ◽  
Stimulation Of

Intracellular [Ca] ([Ca]i) was measured following secretagogue stimulation of rabbit gastric glands loaded with the Ca-sensitive dye fura-2. Glands were mounted on cover slips and placed either in a perfused cuvette (for spectrofluorimetric measurements on whole glands) or in a chamber on the stage of a microscope (for microspectrofluorimetric measurements on single parietal cells within a gland). In parietal cells resting [Ca]i = 91 nM. Either histamine or carbachol caused [Ca]i to increase (spike) rapidly (within 5 s) to greater than 425 nM by releasing Ca from an intracellular store. The two hormones acted on the same store, with carbachol being the more potent releaser. The spike occurred equally well in solutions containing the Ca channel blockers verapamil, nifedipine, Co, or La. After the spike, [Ca]i decreased to a plateau level (130-200 nM) that was dependent on the presence of secretagogue but was independent from the release of the intracellular store. This plateau persisted (up to 40 min) until the addition of antagonist or until the removal of either extracellular Ca or the agonist. Histamine and carbachol were specifically blocked by the H2-antagonist cimetidine and the muscarinic antagonist atropine, respectively. Histamine often induced repeated increases in [Ca]i. A combination of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) had no effect on [Ca]i, but if cells were pretreated with histamine, DBcAMP + IBMX would cause [Ca]i to increase. Because exposure to DBcAMP + IBMX stimulates acid secretion yet does not affect [Ca]i, two independent pathways to acid secretion may exist.

Functional heterogeneity of parietal cells along the pig-gland axis

1997 ◽  
Vol 272 (1) ◽  
pp. G161-G171 ◽  
Author(s):  
S. M. Karam ◽  
X. Yao ◽  
J. G. Forte
Keyword(s):  
Acid Secretion ◽  
Gastric Gland ◽  
Longitudinal Axis ◽  
Parietal Cells ◽  
Gastric Epithelium ◽  
Functional Heterogeneity ◽  
Gastric Glands ◽  
Isolated Gastric Glands ◽  
Morphological Transformations ◽  
Stimulation Of

The gastric epithelium forms numerous short pits continuous with long tubular glands divisible into isthmus neck, and base regions. Parietal cells are produced in the isthmus and migrate down to the neck and base regions as they mature and age. Stimulation of parietal cells is manifested by translocation of H(+)-K(+)-adenosinetriphosphatase-rich tubulovesicles (TV) from the cytoplasm into the secretory-apical (SA) membrane. In this study we used rabbit isolated gastric glands to examine the physiological responses of parietal cells to graded levels of stimulation. Quantitative morphometry was used to evaluate parietal cell response along the longitudinal axis of the gland. Acid secretion as estimated by [14C]aminopyrine uptake was well correlated with parallel enzymatic and immunoblot assays for the redistribution of H(+)-K(+)-ATPase from TV to SA membranes. These responses also correlated well with morphological transformations of parietal cells within the isthmus and neck regions of the gastric gland; however, parietal cells in the base of the gland showed very little morphological change in response to any of the stimuli used. The poor responsiveness of basal parietal cells is in agreement with observations of intact mucosa and suggests that older parietal cells may serve some function other than acid secretion.

Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway

1996 ◽  
Vol 270 (4) ◽  
pp. G619-G633 ◽  
Author(s):  
M. Hocker ◽  
Z. Zhang ◽  
D. A. Fenstermacher ◽  
S. Tagerud ◽  
M. Chulak ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Histidine Decarboxylase ◽  
Peptide Hormone ◽  
Direct Stimulation ◽  
Gastric Glands ◽  
Kinase C ◽  
Translational Start ◽  
Stimulation Of

The enzyme L-histidine decarboxylase (HDC; EC 4.1.1.22), which converts L-histidine to histamine, plays a key role in the regulation of acid secretion. In the rat and human stomach, the peptide hormone gastrin appears to be one of the main regulators of HDC expression. In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole. In situ hybridization revealed that HDC expression occurred in the basal third of gastric glands where enterochromaffin-like cells are localized. To study the regulation of HDC gene transcription, 1,291 nucleotides of the 5'-flanking region of the rat HDC gene and the noncoding portion of exon 1 were cloned and sequenced. Gastrin and cholecystokinin (CCK) octapeptide equipotently stimulated the transcriptional activity of the rat HDC promoter three- to fourfold, and deletion analysis revealed the presence of a gastrin response element within 201 nucleotides upstream of the translational start site. Time-course studies revealed maximal activation of the HDC promoter after 12-36 h. Direct stimulation of protein kinase C (PKC) with the phorbol ester phorbol 12-myristate 13-acetate (PMA) substantially elevated rat HDC promoter activity, whereas induction of Ca2+ -dependent signaling pathways with thapsigargin was without effect. Downregulation or blockade of PKC abolished the effects of gastrin and PMA on the HDC promoter. These data indicate that stimulation of the CCK-B/gastrin receptor activates the rat HDC promoter in a time- and dose-dependent fashion and that this effect is primarily mediated via a PKC-dependent signaling pathway. Use of HDC as a model gene will allow further investigation of the intracellular pathways that are involved in gastrin-dependent gene regulation.

scholarly journals Comparative Histological Study of the Stomach in Two Species of Iraqi Vertebrates (Magpie Pica pica L. and Small Asian Mongoose Herpestes javanicus E.)

2019 ◽  
Vol 16 (2) ◽  
pp. 0281
Author(s):  
AL –Nakeeb Et al.
Keyword(s):  
Outer Layer ◽  
Histological Study ◽  
Gastric Gland ◽  
Parietal Cells ◽  
Pica Pica ◽  
Gastric Glands ◽  
Chief Cells ◽  
Herpestes Javanicus ◽  
Mucous Neck Cells ◽  
Muscularis Externa

          A histological study showed the wall of the stomach in Pica pica and Herpestes javanicus consists of four layers: mucosa, submucosa, muscularis externa and serosa. Also, the present study showed many  differences in the histological structures of the stomach for each in both types. The stomach of P. pica consists of two portions: the proventiculus and gizzard, while the stomach of H. javanicus consists of three portions: cardiac, fundic and pyloric regions. The mucosa layer formed short gastric folds, named plicae. In the proventiculus of P. pica, sulcus is found between each two plicae, but the folds called gastric pits in the gizzard, which are full with koilin. Lamina properia in both types contained gastric glands (straight simple tubular glands) named superficial glands, as well as another gastric gland found in the submucosa layer of the proventiculus in P. pica only named deep gastric glands. The gastric gland in the stomach of H. javanicus contained: mucous neck cells and parietal cells positive to AB/PAS stains in cardiac portion, as well as chief cells in fundic portion, but pyloric portion had just mucous neck cells. Muscularis externa in both types formed two muscle layers: inner and outer layer.

Gastric and duodenal HCO3- transport in vitro: effects of hormones and local transmitters

1982 ◽  
Vol 242 (2) ◽  
pp. G100-G110 ◽  
Author(s):  
G. Flemstrom ◽  
J. R. Heylings ◽  
A. Garner
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Duodenal Mucosa ◽  
Dibutyryl Camp ◽  
Inhibitory Peptide ◽  
Luminal Membrane ◽  
Wide Range ◽  
In Vitro Effects ◽  
Histamine H2 Antagonists ◽  
Stimulation Of

Luminal application of acid was recently shown to stimulate surface epithelial HCO3(-) transport in stomach and duodenum. Effects of some potential transmitters of this response were therefore studied in amphibian gastric fundic and proximal duodenal mucosa in vitro. Duodenal HCO3- transport, which could be titrated directly, was stimulated by dibutyryl cAMP (DBcAMP, 10(-6) M), the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-6) M), noradrenaline (10(-6) M), pancreatic glucagon (10(-8) M), and gastric inhibitory peptide (GIP, 10(-10) M). Stimulation by glucagon, but not by prostaglandin E2 (PGE2, 10(-6) M), required Cl- in the luminal solution and was prevented by furosemide (10(-3) M). This suggests that glucagon may affect HCO3(-)-Cl- exchange at the luminal membrane while transport stimulated by prostaglandins may be electrogenic. Stimulatory effects of glucagon and PGE2 were also additive. Gastric HCO3- transport, studied in tissues after inhibition of H+ secretion by histamine H2-antagonists, clearly differed from duodenum in that noradrenaline and GIP were inhibitory and DBcAMP was without effect. Stimulation of gastric HCO3- transport was observed with glucagon (10(-8) M), natural cholecystokinin (CCK, 10(-8) M), and CCK octapeptide (10(-7) M), CCK preparations had no effect in the duodenum. Although tested over a wide range of concentrations, no effect on either duodenal or gastric HCO3- transport was observed with histamine, pentagastrin, tetragastrin, urogastrone, ACTH, bombesin, motilin, secretin, serotonin, somatostatin, substance P, or vasoactive intestinal peptide.

Ezrin-calpain I interactions in gastric parietal cells

1993 ◽  
Vol 265 (1) ◽  
pp. C36-C46 ◽  
Author(s):  
X. Yao ◽  
A. Thibodeau ◽  
J. G. Forte
Keyword(s):  
Parietal Cell ◽  
Cell Function ◽  
Gastric Gland ◽  
Cysteine Protease Inhibitor ◽  
Secretory Process ◽  
Breakdown Product ◽  
Gastric Glands ◽  
Wide Range ◽  
Dependent Protein ◽  
Protease Degradation

Gastric ezrin, a membrane-cytoskeletal linker with sequence homology to talin and erythrocyte band 4.1, has been associated with the remodeling of parietal cell apical membrane that occurs with adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase stimulation. Here we examine the interrelationship between parietal cell ezrin and Ca(2+)-dependent protease activity. Addition of Ca2+ to sonicated gastric gland preparations rendered a relatively selective proteolysis of the 80-kDa ezrin, accompanied by the appearance of a 55-kDa breakdown product. Ca(2+)-dependent proteolysis of ezrin was blocked by E64, a cysteine protease inhibitor, or calpastatin, indicating calpain as the responsible protease. Degradation of ezrin in intact gastric glands was achieved by varying extracellular [Ca2+] and [ionomycin]. Ezrin degradation in situ was rapid and relatively selective, although Ca(2+)-dependent degradation of some spectrin-like bands was also observed. The effect of activated calpain I on parietal cell function was assessed by probing the secretory response to histamine stimulation using [14C]aminopyrine uptake, along with parallel measurements of calpain activity, over a wide range of ionomycin. Activation of calpain, as evidenced by loss of parietal cell ezrin, was correlated with decreased AP uptake by stimulated gastric glands, supporting a role for ezrin in the oxyntic secretory process. The calpain-ezrin interaction established here, and the similarities of calpain with talin and erythrocyte band 4.1, suggest a common feature to this family of ezrin/band 4.1/talin proteins that have been implicated in membrane-cytoskeletal association.

Coupling of H(+)-K(+)-ATPase activity and glucose oxidation in gastric glands

1990 ◽  
Vol 258 (5) ◽  
pp. G719-G727 ◽  
Author(s):  
J. Fryklund ◽  
K. Gedda ◽  
D. Scott ◽  
G. Sachs ◽  
B. Wallmark
Keyword(s):  
Atpase Activity ◽  
Glucose Oxidation ◽  
Gastric Gland ◽  
Ph Gradient ◽  
Co2 Production ◽  
O2 Consumption ◽  
Gastric Glands ◽  
Major Mechanism ◽  
Stimulation Of

The production of 14CO2 from uniformly labeled glucose was shown to account for the entire increase in histamine-stimulated O2 consumption in rabbit gastric glands when no other substrate was added to the medium. The increased production of CO2 was correlated to the increase in O2 consumption and the accumulation of [14C]-aminopyrine (AP) after stimulation with several secretagogues. Inhibitors of H(+)-K(+)-ATPase reduced the secretagogue-induced increase in CO2 production by greater than 90%, showing that the activity of this enzyme was responsible for the greater part of gastric gland metabolism under stimulated conditions. In contrast to AP accumulation, inhibition of CO2 production by omeprazole, an acid-activated inhibitor of the H(+)-K(+)-ATPase, was not reversed by washing. The reversal of AP accumulation after omeprazole treatment and washing was most likely due to a recruitment of residual pumps bordering a nonacidic space, which had not previously been inhibited by omeprazole. These residual pumps slowly generate a pH gradient and hence AP uptake. Adding NH4+ to gastric glands resulted in a concentration-dependent increase of CO2 production up to the maximal stimulated level but without formation of the pH gradient as measured by AP uptake and loss of the omeprazole inhibition of glucose oxidation. As NH4+ can act as a K+ surrogate for H(+)-K(+)-ATPase, and as NH3 is membrane permeant, full stimulation of CO2 production is evidence that the major mechanism of H(+)-K(+)-ATPase activation in situ is an increase in the KCl permeability of the pump membrane.

Stimulation of acid formation in permeable gastric glands by valinomycin

1988 ◽  
Vol 255 (3) ◽  
pp. G313-G318 ◽  
Author(s):  
S. J. Hersey ◽  
L. Steiner
Keyword(s):  
Parietal Cells ◽  
Acid Formation ◽  
Dependent Manner ◽  
Weak Base ◽  
Gastric Glands ◽  
Concentration Dependent Manner ◽  
Threefold Increase ◽  
Anion Permeability ◽  
Isolated Gastric Glands ◽  
Stimulation Of

Isolated gastric glands made permeable with digitonin treatment were employed to study the ionic requirements of acid formation. Acid formation was monitored by the accumulation of a novel weak base probe, [14C]benzylamine. ATP-dependent acid formation was found to require K+ in a concentration-dependent manner, with an apparent K0.5 = 7 mM. The anion dependence of acid formation gave a selectivity sequence of Cl = I greater than Br greater than NO3 greater than SO4 = isethionate, with isethionate being approximately 50% as effective as Cl. The dependence of acid formation on [Cl] gave an apparent K0.5 = 6 mM. Addition of the K+ ionophore, valinomycin, to resting glands (cimetidine pretreatment) resulted in a two- to threefold increase in ATP-dependent acid formation. In contrast, stimulated (forskolin pretreated) glands showed a greater accumulation of benzylamine with ATP but significantly less valinomycin stimulation. The valinomycin stimulation required both K+ and Cl- and was inhibited by omeprazole and Sch 28080. The results are interpreted to indicate that major events in the transition from a resting to a stimulated state include changes in both K+ and anion permeability of the secretory membrane of parietal cells.

scholarly journals Rab11a redistributes to apical secretory canaliculus during stimulation of gastric parietal cells

1998 ◽  
Vol 275 (1) ◽  
pp. C163-C170 ◽  
Author(s):  
Benjamin C. Calhoun ◽  
Lynne A. Lapierre ◽  
Catherine S. Chew ◽  
James R. Goldenring
Keyword(s):  
Plasma Membranes ◽  
Secretory Granules ◽  
Membrane Vesicle ◽  
Primary Cultures ◽  
Parietal Cells ◽  
Apical Plasma Membrane ◽  
Rab Proteins ◽  
Gastric Glands ◽  
Gastric Parietal Cell ◽  
Stimulation Of

Previous investigations in several systems have demonstrated that Rab3 family members redistribute to soluble fractions on fusion of secretory granules with target plasma membranes. Rab proteins are then recycled back onto mature secretory vesicles after reinternalization of the membrane. Although this cycle is well established for Rab3, far less is known about redistribution of other Rab proteins during vesicle fusion and recycling. In the gastric parietal cell, Rab11a is associated with H-K-ATPase-containing tubulovesicles, which fuse with the apical plasma membrane (secretory canaliculus) in response to agonists such as histamine. We have analyzed distribution of Rab11a and other tubulovesicle proteins in resting and histamine-stimulated rabbit parietal cells. Stimulation of isolated gastric glands in the presence of 100 μM histamine and 100 μM 3-isobutyl-1-methylxanthine did not cause a significant increase in soluble Rab11a. H-K-ATPase, Rab11a, Rab25, syntaxin 3, and SCAMPs increased immunoreactivity in stimulus-associated vesicles prepared from rabbits treated with histamine compared with those from ranitidine-treated animals. The large GTPase dynamin was found in both vesicle preparations, but there was no change in amount of immunoreactivity. Immunofluorescence staining of resting and histamine-stimulated primary cultures of parietal cells demonstrated redistribution of H-K-ATPase and Rab11a to F-actin-rich canalicular membranes. Dynamin was present on canalicular membranes in resting and stimulated cells. These results indicate that Rab11a does not cycle off the membrane during the process of tubulovesicle fusion with the secretory canaliculus. Thus Rab11a may remain associated with recycling apical membrane vesicle populations.

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