EGF and BMPs govern differentiation and patterning in human gastric glands

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.

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Demonstration of gap junctional protein connexin 32 and connexin 26 among parietal cells of mammalian gastric glands

Gastroenterology ◽

10.1016/s0016-5085(98)84762-8 ◽

1998 ◽

Vol 114 ◽

pp. A1171

Author(s):

Gilbert R. Ortega ◽

Rosh Caroppo ◽

Edgar B. Rodas ◽

Athar M. Qureshi ◽

David C. Spray ◽

...

Keyword(s):

Parietal Cells ◽

Connexin 26 ◽

Connexin 32 ◽

Gastric Glands ◽

Junctional Protein ◽

Gap Junctional

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00230.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. G1061-G1066 ◽

Cited By ~ 16

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.

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Helicobacter pyloricytotoxin VacA increases alkaline secretion in gastric epithelial cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.6.g1440 ◽

2001 ◽

Vol 281 (6) ◽

pp. G1440-G1448 ◽

Cited By ~ 19

Author(s):

Lucantonio Debellis ◽

Emanuele Papini ◽

Rosa Caroppo ◽

Cesare Montecucco ◽

Silvana Curci

Keyword(s):

Apical Membrane ◽

Acid Output ◽

Human Infection ◽

Gastric Epithelium ◽

Secondary Development ◽

Acute Effects ◽

Gastric Diseases ◽

Gastric Glands ◽

Frog Stomach ◽

Alkaline Secretion

Human infection by the bacterium Helicobacter pylori (Hp) may lead to severe gastric diseases by an ill-understood process involving several virulence factors. Among these, the cytotoxin VacA is associated with higher tissue damage. In this study, the isolated frog stomach model was used to characterize the acute effects of VacA on the gastric epithelium. Our results show that VacA partially inhibits gastric acid output by increasing HCO[Formula: see text] efflux. Experiments conducted with double-barrelled pH or Cl−-selective microelectrodes on surface epithelial gastric cells (SECs) and single gastric glands show that VacA does not impair the activity of the oxyntic cells but renders the apical membrane of SECs more permeable to HCO[Formula: see text] and Cl−. Inhibition of this permeation by 5-nitro-2-(3-phenylpropylamino) benzoic acid indicates that this may be due to the formation of anion-selective pores by the toxin. We suggest that VacA-dependent HCO[Formula: see text] efflux from SECs improves the environmental conditions (pH, CO2concentration) of the niche parasitized by Hp, that is the gastric surface. This may favor Hp persistence in the tissue and the secondary development of a chronic inflammation.

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Inhibition of acid secretion in isolated gastric glands by substituted benzimidazoles

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1982.243.6.g505 ◽

1982 ◽

Vol 243 (6) ◽

pp. G505-G510 ◽

Cited By ~ 3

Author(s):

E. Fellenius ◽

B. Elander ◽

B. Wallmark ◽

H. F. Helander ◽

T. Berglindh

Keyword(s):

Oxygen Consumption ◽

Gastric Gland ◽

Acid Formation ◽

Gastric Glands ◽

New Class ◽

Weak Bases ◽

Morphological Studies ◽

Isolated Gastric Glands ◽

Dose Dependent ◽

Distal Site

A new class of gastric acid inhibitors, substituted benzimidazoles (H 83/69 and H 149/94), have been tested in an isolated rabbit gastric gland preparation. Acid formation in the glands was stimulated by histamine, dibutyryl cAMP (DBcAMP), and high extracellular K+ concentrations, and the glandular secretory response was measured by changes in oxygen consumption and in accumulation of the weak base [14C]aminopyrine (AP). The substituted benzimidazoles inhibited AP accumulation induced by all stimulants in a dose-dependent noncompetitive manner. In contrast, cimetidine only inhibited histamine-induced AP accumulation. Basal AP accumulation, not affected by cimetidine, was also inhibited by the substituted benzimidazoles, as was the increase in glandular oxygen consumption produced by the addition of histamine and DBcAMP. Basal oxygen consumption was inhibited by about 15%. The substituted benzimidazoles, like AP, are weak bases and were also found to accumulate in the glands. Semiquantitative morphological studies of glands stimulated by histamine plus theophylline did not show any change in the enlarged secretory surface area after stimulation in the presence of inhibitory concentrations of H 149/94 (10(-4) M). The results suggest that substituted benzimidazoles have a mechanism of action different from that of H2-receptor antagonists and indicate a very distal site of action in the events leading to acid formation.

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Ontogeny of pepsin secretory response to secretagogues in isolated rat gastric glands

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.250.2.g200 ◽

1986 ◽

Vol 250 (2) ◽

pp. G200-G204 ◽

Cited By ~ 3

Author(s):

J. Yahav ◽

P. C. Lee ◽

E. Lebenthal

Keyword(s):

Term Neonate ◽

Ionophore A23187 ◽

Newborn Rats ◽

Dibutyryl Camp ◽

Gastric Glands ◽

Cholecystokinin Octapeptide ◽

Rat Pups ◽

Isolated Gastric Glands ◽

Old Rats ◽

Isolated Rat

By use of isolated gastric glands from rats at various ages, we demonstrated that full-term neonate and 1-day-old rats showed no response to cholecystokinin octapeptide (CCK-OP), carbachol, or Ca2+ ionophore. The same glands, however, were responsive to dibutyryl cAMP. A mature response was not found until the pups were 2 days old. Injection of hydrocortisone into newborn rats led to an increase in pepsinogen concentrations in gastric glands and also an increased responsiveness to CCK-OP, carbachol, and Ca2+ ionophore A23187 24 h after administration. Hydrocortisone thus caused precocious maturation of both pepsinogen accumulation and pepsinogen secretory responsiveness of gastric glands in rat pups.

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Uremic Gastropathy in the Dog

Veterinary Pathology ◽

10.1177/030098587901600303 ◽

1979 ◽

Vol 16 (3) ◽

pp. 292-309 ◽

Cited By ~ 26

Author(s):

N. F. Cheville

Keyword(s):

Endoplasmic Reticulum ◽

Lamina Propria ◽

Vascular Injury ◽

Parietal Cell ◽

Cell Function ◽

Gastric Glands ◽

Cell Content ◽

Calcium Salts ◽

Argentaffin Cell ◽

Mucosal Lamina Propria

Stomachs of four dogs with uremia and four normal dogs were examined. Uremic stomachs represented four types of disease: atrophic, amyloidotic, ulcerative and necrotic gastropathy. Pathologic changes common to all uremic stomachs were expansion of the lamina propria, atrophy of gastric glands, and submucosal arteriopathy; lesions were limited to body and fundic zones. Lamina propria was markedly expanded by edema, mastocytosis, deposition of acidic mucosubstances, fibroplasia and mineralization. Capillaries in lamina propria had swollen endothelium and calcium salts were present extracellularly as amorphous granular laminae. Gastric glands were distorted and irregular and had fewer cells per unit of tissue. Parietal cells were swollen and had fragmentation of cytocavitary network and mitochondrial swelling with calcification. Chief cells were shrunken, agranular and atrophic with foci of glycogen and dilation of endoplasmic reticulum. Argentaffin cell content was diminished. Muscular arteries of submucosae had segmental degenerative lesions characterized by myocyte necrosis, calcification, and deposition of acidic mucosubstances and fibrin; thrombosis and obstructive arteriopathy were common. These studies suggest that uremic gastropathy is a disease of mucosal lamina propria and that lesions were due to anoxia caused by diffuse vascular injury and to altered parietal cell function.

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Luminal perfusion of isolated gastric glands

AJP Cell Physiology ◽

10.1152/ajpcell.1994.266.4.c1013 ◽

1994 ◽

Vol 266 (4) ◽

pp. C1013-C1027 ◽

Cited By ~ 36

Author(s):

S. J. Waisbren ◽

J. Geibel ◽

W. F. Boron ◽

I. M. Modlin

Keyword(s):

Ph Sensitive ◽

Renal Tubules ◽

Gastric Glands ◽

Ph Gradients ◽

Large Size ◽

Isolated Gastric Glands ◽

Buffering Power ◽

Luminal Perfusion ◽

Ethanesulfonic Acid ◽

Fast Perfusion

We have extended to rabbit gastric glands the technique for perfusing single isolated renal tubules. We isolated glands by hand dissection and used concentric glass pipettes to hold them and perfuse their lumina. Parietal cells (PCs), which tended to be located toward the gland opening, were identified by their pyramidal shape, large size, and autofluorescence. Chief cells (CCs) were identified by their round shape and smaller size. In some experiments, we perfused the lumen with hydroxypyrenetrisulfonate, a pH-sensitive fluorophore, at pH 7.4 and used digital image processing to monitor luminal pH (pH1). Solutions were buffered with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid to pH 7.4 at 37 degrees C. With fast perfusion, we found no evidence of decreased pH1, even with stimulation by 10 microM carbachol. With slow perfusion, pH1 often fell below the dye's sensitive range (pH < 5), especially at low perfusate buffering power. In other experiments, we loaded cells with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and monitored intracellular pH (pHi) in multiple individual PCs and CCs in a single gland. Mean pHi was 7.21 +/- 0.02 (n = 136 cells) for PCs and 7.27 +/- 0.03 (n = 103) for CCs. To examine the response to decreased pH1 and basolateral pH (pHb), we lowered pHb to 6.4 or lowered pH1 to 3.4 or 1.4. Lowering pHb to 6.4 for approximately 1 min caused pHi to fall reversibly by 0.39 +/- 0.05 (n = 53) in PCs and 0.58 +/- 0.03 (n = 50) in CCs. Lowering pH1 to 3.4 or 1.4 caused no significant pHi changes in PCs (n = 38 and 82) or in CCs (n = 44 and 77). Carbachol did not affect the response to changes in pH1 or pHb. We conclude that the apical surfaces of PCs and CCs are unusually resistant to extreme pH gradients.

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