Differentiation of the Gastric Mucosa I. Role of histamine in control of function and integrity of oxyntic mucosa: understanding gastric physiology through disruption of targeted genes

2006 ◽  
Vol 291 (4) ◽  
pp. G539-G544 ◽  
Author(s):  
Duan Chen ◽  
Takeshi Aihara ◽  
Chun-Mei Zhao ◽  
Rolf Håkanson ◽  
Susumu Okabe
Keyword(s):  
Gastric Mucosa ◽  
Histidine Decarboxylase ◽  
Parietal Cells ◽  
Oxyntic Mucosa ◽  
Mucosal Integrity ◽  
Ecl Cells ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
Insight Into

Many physiological functions of the stomach depend on an intact mucosal integrity; function reflects structure and vice versa. Histamine in the stomach is synthesized by histidine decarboxylase (HDC), stored in enterochromaffin-like (ECL) cells, and released in response to gastrin, acting on CCK2 receptors on the ECL cells. Mobilized ECL cell histamine stimulates histamine H2 receptors on the parietal cells, resulting in acid secretion. The parietal cells express H2, M3, and CCK2 receptors and somatostatin sst2 receptors. This review discusses the consequences of disrupting genes that are important for ECL cell histamine release and synthesis (HDC, gastrin, and CCK2 receptor genes) and genes that are important for “cross-talk” between H2 receptors and other receptors on the parietal cell (CCK2, M3, and sst2 receptors). Such analysis may provide insight into the functional significance of gastric histamine.

scholarly journals IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

2013 ◽  
Vol 50 (2) ◽  
pp. 157-160 ◽  
Author(s):  
Jand-Venes Rolim MEDEIROS ◽  
Pedro Marcos Gomes SOARES ◽  
Gerly Anne de Castro BRITO ◽  
Marcellus Henrique Loiola Ponte de SOUZA
Keyword(s):  
Gastric Mucosa ◽  
Immunohistochemical Analysis ◽  
Parietal Cells ◽  
Gastric Epithelium ◽  
Gastric Tissue ◽  
Specific Expression ◽  
Ethanol Injection ◽  
Mucosal Integrity ◽  
Gastric Mucosa Damage

Context Hydrogen sulphide (H2S) has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g). After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation

2004 ◽  
Vol 20 (1) ◽  
pp. 131-142 ◽  
Author(s):  
M. Kidd ◽  
T. Hinoue ◽  
G. Eick ◽  
K. D. Lye ◽  
S. M. Mane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Mucosa ◽  
Western Blot ◽  
Cell Transformation ◽  
Mastomys Natalensis ◽  
Rt Pcr ◽  
Cell Hyperplasia ◽  
Ecl Cells ◽  
Ecl Cell ◽  
Gene Expression Alterations

Enterochromaffin-like (ECL) cell hyperplasia and then irreversible neoplasia can be generated in the African rodent Mastomys natalensis using the H2 receptor blocker, loxtidine, for 8–16 wk. We used a GeneChip approach complemented by standard technologies to identify gene expression alterations in the gastric mucosa during gastrin-mediated ECL cell transformation. Gastric mucosa (mucosal scrapping) and ECL cell-enriched fractions were obtained from untreated Mastomys (controls) and from animals treated with loxtidine for 8 wk (hyperplasia). Tumor ECL cells were obtained by hand-dissection of gastric ECL cell nodules from animals treated with loxtidine for >16 wk and from a spontaneously developed ECL cell tumor. RNA was isolated, examined on rat U34A GeneChips, and comparison analysis was performed to identify altered gene expression. Alterations in gene expressions were examined further by immunohistochemistry, quantitative RT-PCR (Q-RT-PCR), sequencing and Western blot. GeneSpring analysis demonstrated alterations in few genes (<20) in hyperplastic and tumor mucosa. The histamine H1 receptor was consistently increased in proliferating mucosa. This gene change was confirmed by Q-RT-PCR. Other genes showing alterations included neural-(chromogranin A and somatostatin), cell-cycle-, and AP-1-associated genes. Immunostaining confirmed alterations in neural markers. Cluster analysis of ECL cell-enriched samples demonstrated that c- fos and junD were differently regulated. Q-RT-PCR and Western blot in prospectively collected gastric mucosal samples confirmed the differential expression of Fos and Jun. The negative regulators of AP-1, JunD, and Menin were decreased in tumor mucosa. A missense of unknown function was noted in the menin gene. Hypergastrinemia in an animal model of gastric carcinoids differentially altered the histamine type 1 receptor and gene expression and protein composition of AP-1. These results suggest that expression of this receptor and an altered composition of AP-1 with a loss of inhibition play a role in ECL cell transformation.

scholarly journals Purification of Gastric Mucosal ECL Cells from a Crude Elutriation Fraction

2002 ◽  
Vol 2 ◽  
pp. 1643-1645 ◽  
Author(s):  
John Graham
Keyword(s):  
Gastric Mucosa ◽  
Ion Transport ◽  
Parietal Cell ◽  
Cell Function ◽  
Parietal Cells ◽  
Centrifugal Elutriation ◽  
Ecl Cells ◽  
Acid Secreting ◽  
Density Barrier

Acid-secreting parietal cells from the gastric mucosa are widely studied as a model in studies on ion transport and the endocrine/paracrine ECL cells effectively control parietal cell function. Discontinuous gradients of iodixanol for the purification of ECL cells were subsequently simplified to the use of a density barrier. This technique is now commonly used following initial centrifugal elutriation.

Ischemia of rat stomach mobilizes ECL cell histamine

2005 ◽  
Vol 288 (5) ◽  
pp. G1084-G1090 ◽  
Author(s):  
Masayuki Kitano ◽  
Maria Bernsand ◽  
Yosuke Kishimoto ◽  
Per Norlén ◽  
Rolf Håkanson ◽  
...  
Keyword(s):  
Histidine Decarboxylase ◽  
Ischemia Reperfusion ◽  
Celiac Artery ◽  
Enzyme Linked Immunosorbent Assay ◽  
Decarboxylase Activity ◽  
Rat Stomach ◽  
Ecl Cells ◽  
Ecl Cell ◽  
Mucosal Lesions ◽  
Histidine Decarboxylase Activity

Microdialysis was used to study how ischemia-evoked gastric mucosal injury affects rat stomach histamine, which resides in enterochromaffin-like (ECL) cells and mast cells. A microdialysis probe was inserted into the gastric submucosa, and the celiac artery was clamped (30 min), followed by removal of the clamp. Microdialysate histamine was determined by enzyme-linked immunosorbent assay. In addition, we studied the long-term effects of ischemia on the oxyntic mucosal histidine decarboxylase activity in omeprazole-treated rats. Gastric mucosal lesions induced by the ischemia were enlarged on removal of the clamp. The microdialysate histamine concentration increased immediately on clamping (50-fold rise within 30 min) and declined promptly after the clamp was removed. In contrast, histidine decarboxylase activity of the ECL cells was lowered by the ischemia and returned to preischemic values 9 days later. Mast cell-deficient rats responded to ischemia-reperfusion much like wild-type rats with respect to histamine mobilization. Pretreatment with the irreversible inhibitor of histidine decarboxylase, α-fluoromethylhistidine, which is known to eliminate histamine from ECL cells, prevented the rise in microdialysate histamine. Pharmacological blockade of acid secretion (cimetidine or omeprazole) prevented the lesions induced by ischemia-reperfusion insult but not the mobilization of histamine. In conclusion, ischemia of the celiac artery mobilizes large amounts of histamine from ECL cells, which occurs independently of the gross mucosal lesions. The prompt reduction of the mucosal histidine decarboxylase activity in response to ischemia probably reflects ECL cell damage. The lesions develop not because of mobilization of histamine per se but because of ischemia plus reperfusion plus gastric acid.

Differentiation of the Gastric Mucosa II. Role of gastrin in gastric epithelial cell proliferation and maturation

2006 ◽  
Vol 291 (5) ◽  
pp. G762-G765 ◽  
Author(s):  
Renu N. Jain ◽  
Linda C. Samuelson
Keyword(s):  
Genetically Engineered ◽  
Gastric Epithelial Cells ◽  
Balanced Growth ◽  
Cellular Targets ◽  
Genetically Engineered Mouse Models ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
Acid Secreting ◽  
And Function

Gastrin is the principal hormonal inducer of gastric acid secretion. The cellular targets for gastrin in the stomach are the acid-secreting parietal cell and histamine-producing enterochromaffin-like (ECL) cell. Gastrin is also a growth factor, with hypergastrinemia resulting in increased proliferation of gastric progenitor cells and a thickened mucosa. This review presents insights into gastrin function revealed by genetically engineered mouse models, demonstrating a new role for gastrin in the maturation of parietal and ECL cells. Thus, gastrin regulates many aspects of gastric physiology, with tight regulation of gastrin levels required to maintain balanced growth and function of gastric epithelial cells.

scholarly journals Towards Understanding of Gastric Cancer Based upon Physiological Role of Gastrin and ECL Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3477
Author(s):  
Helge Waldum ◽  
Patricia Mjønes
Keyword(s):  
Gastric Juice ◽  
Physiological Role ◽  
Easy Access ◽  
Gastric Adenocarcinomas ◽  
Gastric Physiology ◽  
Ecl Cell ◽  
A Cell ◽  
Increased Sensitivity ◽  
Main Regulator

The stomach is an ideal organ to study because the gastric juice kills most of the swallowed microbes and, thus, creates rather similar milieu among individuals. Combined with a rather easy access to gastric juice, gastric physiology was among the first areas to be studied. During the last century, a rather complete understanding of the regulation of gastric acidity was obtained, establishing the central role of gastrin and the histamine producing enterochromaffin-like (ECL) cell. Similarly, the close connection between regulation of function and proliferation became evident, and, furthermore, that chronic overstimulation of a cell with the ability to proliferate, results in tumour formation. The ECL cell has long been acknowledged to give rise to neuroendocrine tumours (NETs), but not to play any role in carcinogenesis of gastric adenocarcinomas. However, when examining human gastric adenocarcinomas with the best methods presently available (immunohistochemistry with increased sensitivity and in-situ hybridization), it became clear that many of these cancers expressed neuroendocrine markers, suggesting that some of these tumours were of neuroendocrine, and more specifically, ECL cell origin. Thus, the ECL cell and its main regulator, gastrin, are central in human gastric carcinogenesis, which make new possibilities in prevention, prophylaxis, and treatment of this cancer.

PACAP and gastrin regulate the histidine decarboxylase promoter via distinct mechanisms

2004 ◽  
Vol 286 (1) ◽  
pp. G51-G59 ◽  
Author(s):  
John T. McLaughlin ◽  
Wandong Ai ◽  
Natalie F. Sinclair ◽  
Rocchina Colucci ◽  
Raktima Raychowdhury ◽  
...  
Keyword(s):  
Potential Role ◽  
Cell Function ◽  
Histidine Decarboxylase ◽  
Adenyl Cyclase ◽  
Luciferase Reporter ◽  
Promoter Activation ◽  
Ecl Cell ◽  
Pituitary Adenylate Cyclase

The enterochromaffin-like (ECL) cell controls gastric acid secretion via histamine, generated by l-histidine decarboxylase (HDC). HDC expression is regulated by gastrin. However, gastrin is not alone in controlling ECL cell function. For example, the neural peptide pituitary adenylate cyclase-activating polypeptide (PACAP) also increases ECL cell proliferation. To investigate a potential role of PACAP in regulating HDC expression, we generated a series of HDC promoter-luciferase reporter constructs and transiently transfected them into PC12 cells (stably expressing the gastrin-CCK-2 receptor). We found that PACAP regulates HDC promoter activity. This is temporally biphasic, involving both adenyl cyclase and phospholipase C-dependent pathways. Deletional analysis, block mutation, and EMSA demonstrated a PACAP-response element at -177 to -170, wholly necessary for the effects of PACAP and discrete from known gastrin-responsive elements. Discrete neural and endocrine pathways regulate ECL cells through different patterns of postreceptor signaling and promoter activation, which may be appropriate to their functions in vivo.

Immunolocalization of gastrin-dependent histidine decarboxylase activity in rat gastric mucosa during feeding

1998 ◽  
Vol 275 (4) ◽  
pp. G660-G667 ◽  
Author(s):  
Gordon V. Ohning ◽  
Min Song ◽  
Helen C. Wong ◽  
S. Vincent Wu ◽  
John H. Walsh
Keyword(s):  
Enzyme Activity ◽  
Histidine Decarboxylase ◽  
Gastric Gland ◽  
Decarboxylase Activity ◽  
Rapid Reduction ◽  
Oxyntic Mucosa ◽  
Ecl Cells ◽  
Rat Gastric Mucosa ◽  
Fasting And Refeeding ◽  
Atropine Treatment

The localization of histidine decarboxylase (HDC) activity in the enterochromaffin-like (ECL) cells of the oxyntic mucosa was studied during fasting and refeeding using monoclonal (CURE no. 44178) and polyclonal (CURE no. 94211) antibodies directed against the COOH terminus of HDC (HDC-CT). Changes in HDC immunostaining were correlated with mucosal HDC enzyme activity. Immunoneutralization of circulating gastrin and atropine treatment during refeeding were used to determine the relative importance of gastrin and cholinergic mechanisms in the regulation of HDC activity and immunostaining. Fasting caused a rapid reduction in the number of ECL cells immunostaining for HDC that was correlated with an almost complete loss of mucosal HDC enzyme activity. Refeeding restored both HDC immunostaining and enzyme activity within 2–4 h, and this response was inhibited by gastrin immunoneutralization but not by atropine treatment. Immunostaining was uniformly decreased and restored in the lower half of the oxyntic mucosa, which corresponds to the predominant area of ECL cells in the gastric gland. Histamine immunostaining and mucosal histamine content were not significantly changed during fasting and refeeding or by gastrin antibody and/or atropine treatment during refeeding. These findings indicate that HDC activity correlates with HDC-CT immunostaining and that both HDC activity and HDC-CT immunostaining are regulated by gastrin during refeeding.

Gastrin stimulation of histamine synthesis in enterochromaffin-like cells from rabbit fundic mucosa

1996 ◽  
Vol 270 (3) ◽  
pp. G463-G469 ◽  
Author(s):  
F. Hollande ◽  
S. Combettes ◽  
J. P. Bali ◽  
R. Magous
Keyword(s):  
Histidine Decarboxylase ◽  
Polymyxin B ◽  
Maximal Velocity ◽  
Dependent Manner ◽  
Ecl Cells ◽  
Histamine Synthesis ◽  
Mucosal Cells ◽  
Enzyme Molecules ◽  
Stimulation Of

This work aimed to investigate the molecular role of gastrin in histamine synthesis in isolated rabbit fundic mucosal cells enriched in enterochromaffin-like (ECL) cells (37%). Gastrin stimulated histidine decarboxylase (HDC) activity by increasing the maximal velocity (Vmax) from 0.240 +/- 0.017 (basal value) to 0.332 +/- 0.012 pmol/mg protein/h and by decreasing the Michaelis-Menten constant value -Km; 73.90 +/- 2.2 vs. 93.42 +/- 4.32 microM (basal value)]. Pertussis toxin (PTX) (200 ng/ml) reduced the stimulation of HDC induced by 10 nM gastrin from 41.8 to 15.9%, whereas cholera toxin (CTX) (100 ng/ml) was without effect. Staurosporine and polymyxin B inhibited in a dose dependent manner the HDC activity stimulated by 10 nM gastrin. Phorbol 12-myristate 13-acetate (PMA; 100 nM) decreased Vmax (0.558 +/- 0.021 pmol/ mg protein/h) but did not change the Km. Furthermore, cycloheximide (0.1-10 microM) inhibited the gastrin-induced stimulation of HDC activity, whereas actinomycin D (up to 10 microM) was without effect. Finally, incubation of cells with gastrin (10 microM) left the expression of HDC mRNA unchanged. We concluded that gastrin, acting through "gastrin/CCK-B type" receptors coupled to PTX-sensitive G protein, exerts a short-term regulation of histamine synthesis in gastric ECL cells by increasing both the affinity of HDC for L-histidine and the number of active enzyme molecules. This last event, related to protein kinase C activation, could be due to a translational or posttranslational mechanism.

Extracts of ECL-cell granules/vesicles and of isolated ECL cells from rat oxyntic mucosa evoke a Ca2+ second messenger response in osteoblastic cells

2001 ◽  
Vol 97 (2-3) ◽  
pp. 153-161 ◽  
Author(s):  
Birgitta Larsson ◽  
Amel Gritli-Linde ◽  
Per Norlén ◽  
Erik Lindström ◽  
Rolf Håkanson ◽  
...  
Keyword(s):  
Second Messenger ◽  
Osteoblastic Cells ◽  
Oxyntic Mucosa ◽  
Ecl Cells ◽  
Ecl Cell
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