scholarly journals NHE8 plays important roles in gastric mucosal protection

2013 ◽  
Vol 304 (3) ◽  
pp. G257-G261 ◽  
Author(s):  
Hua Xu ◽  
Jing Li ◽  
Huacong Chen ◽  
Chunhui Wang ◽  
Fayez K. Ghishan
Keyword(s):  
Gastric Ulcer ◽  
Physiological Role ◽  
Mucosal Surface ◽  
Sodium Absorption ◽  
Bicarbonate Secretion ◽  
Mucosal Protection ◽  
Mucous Cells ◽  
Gastric Glands ◽  
Surface Ph ◽  
Gastric Mucosal Protection

Sodium/hydrogen exchanger (NHE) 8 is an apically expressed membrane protein in the intestinal epithelial cells. It plays important roles in sodium absorption and bicarbonate secretion in the intestine. Although NHE8 mRNA has been detected in the stomach, the precise location and physiological role of NHE8 in the gastric glands remain unclear. In the current study, we successfully detected the expression of NHE8 in the glandular region of the stomach by Western blotting and located NHE8 protein at the apical membrane in the surface mucous cells by a confocal microscopic method. We also identified the expression of downregulated-in-adenoma (DRA) in the surface mucous cells in the stomach. Using NHE8−/− mice, we found that NHE8 plays little or no role in basal gastric acid production, yet NHE8−/− mice have reduced gastric mucosal surface pH and higher incidence of developing gastric ulcer. DRA expression was reduced significantly in the stomach in NHE8−/− mice. The propensity for gastric ulcer, reduced mucosal surface pH, and low DRA expression suggest that NHE8 is indirectly involved in gastric bicarbonate secretion and gastric mucosal protection.

scholarly journals Impaired mucin synthesis and bicarbonate secretion in the colon of NHE8 knockout mice

2012 ◽  
Vol 303 (3) ◽  
pp. G335-G343 ◽  
Author(s):  
Hua Xu ◽  
Bo Zhang ◽  
Jing Li ◽  
Chunhui Wang ◽  
Huacong Chen ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Physiological Role ◽  
Normal Serum ◽  
Sodium Absorption ◽  
Bicarbonate Secretion ◽  
Embryonic And Fetal Development ◽  
Sodium Hydrogen Exchanger ◽  
Important Player ◽  
Normal Serum Sodium

Sodium/hydrogen exchanger 8 (NHE8), the newest member of the SLC9 family, is expressed at the apical membrane of the epithelial cells in the intestine and the kidney. Although NHE8 has been shown to be an important player for intestinal sodium absorption early in development, its physiological role in the intestine remains unclear. Here, we successfully created a NHE8 knockout (NHE8−/−) mouse model to study the function of this transporter in the intestinal tract. Embryonic stem cells containing interrupted NHE8 gene were injected into mouse blastocyst to produce NHE8+/− chimeras. NHE8−/− mice showed no lethality during embryonic and fetal development. These mice had normal serum sodium levels and no signs of diarrhea. Apically expressed NHE2 and NHE3 were increased in the small intestine of the NHE8−/− mice in compensation. The number of goblet cells and mucin (MUC)-positive cells in the colon was reduced in NHE8−/− mice along with mucosal pH, MUC2 expression as well as downregulated in adenoma (DRA) expression. Therefore, the role of NHE8 in the intestine involves both sodium absorption and bicarbonate secretion.

Nonprotein sulfhydryl compounds in canine gastric mucosa: effects of PGE2 and ethanol

1985 ◽  
Vol 249 (1) ◽  
pp. G137-G144 ◽  
Author(s):  
T. A. Miller ◽  
D. Li ◽  
Y. J. Kuo ◽  
K. L. Schmidt ◽  
L. L. Shanbour
Keyword(s):  
Gastric Mucosa ◽  
Low Dose ◽  
Mucosal Damage ◽  
Gastric Mucosal Damage ◽  
High Dose ◽  
Mucosal Protection ◽  
Gastric Mucosal Protection ◽  
Sulfhydryl Compounds ◽  
Mild Irritants

By use of an in vivo canine chambered stomach preparation in which the gastric mucosa was partitioned into two equal halves, the effect of topical 16,16-dimethyl PGE2 (DMPGE2) (1 microgram/ml of perfusate) and 8% and 40% ethanol on tissue levels of nonprotein sulfhydryl compounds was assessed. Both DMPGE2 and 8% ethanol significantly increased (P less than 0.005) mucosal levels of nonprotein sulfhydryls when compared with corresponding mucosa bathed with saline alone. In contrast, mucosa bathed with 40% ethanol showed significantly decreased levels. If mucosa was bathed with DMPGE2 or 8% ethanol prior to exposing the stomach to 40% ethanol, this depletion in sulfhydryl compounds was not observed. Since other experimental observations have shown that exogenously administered prostaglandins and mild irritants (such as low-dose alcohol) can prevent gastric mucosal damage by necrotizing agents (such as high-dose alcohol), our findings are consistent with the hypothesis that nonprotein sulfhydryls may play a role in mediating gastric mucosal protection.

Development of sensitivity to cAMP-inducing hormones in the rat stomach

1984 ◽  
Vol 247 (3) ◽  
pp. G231-G239
Author(s):  
C. Gespach ◽  
Y. Cherel ◽  
G. Rosselin
Keyword(s):  
Biological Activities ◽  
Physiological Role ◽  
H2 Receptor Antagonist ◽  
Adult Rats ◽  
Gastric Glands ◽  
Camp Generation ◽  
Final Maturation ◽  
Noncompetitive Inhibitor ◽  
Regulatory Properties

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.

scholarly journals Role of gap junctions in gastric mucosal protection.

1993 ◽  
Vol 61 ◽  
pp. 107
Author(s):  
Fujsao Ueda ◽  
Kiyotaka Mimura ◽  
Shin-ichi Tsuchiya ◽  
Kiyoshi Kimura
Keyword(s):  
Gap Junctions ◽  
Mucosal Protection ◽  
Gastric Mucosal Protection

Mesolimbic dopamine mediates gastric mucosal protection by central neurotensin

1991 ◽  
Vol 260 (1) ◽  
pp. G34-G38 ◽  
Author(s):  
L. P. Xing ◽  
C. Balaban ◽  
J. Seaton ◽  
J. Washington ◽  
G. Kauffman
Keyword(s):  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Acid Secretion ◽  
Lateral Ventricle ◽  
Cold Water ◽  
Mucosal Injury ◽  
Mucosal Protection ◽  
Minimal Effective Dose ◽  
Gastric Mucosal Protection ◽  
6 Hydroxydopamine

Bilateral microinjection (1.0 microliter/side) of neurotensin (NT; 0.3, 1.5, and 3.0 micrograms/side) into the nucleus accumbens (NACB) and ventral tegmental area (VTA) but not in substantia nigra and striatum reduced gastric mucosal injury produced by 2 h of cold-water restraint (CWR). The minimal effective dose for NT-induced protection was 10-100 times lower when administered directly into NACB than into the lateral ventricle. These effects were blocked by pretreatment with the dopamine (DA) receptor antagonist, haloperidol (Hal; 0.5 microgram/side) given directly into NACB. Injection of 6-hydroxydopamine into VTA depleted endogenous DA and inhibited gastric mucosal protection against CWR-induced injury afforded by NT pretreatment. NT, given into either VTA and NACB, inhibited pentagastrin-stimulated gastric acid secretion. These results suggest that VTA and NACB, which represent the mesolimbic DA system, are important locations for interaction between NT and DA receptors to produce gastric mucosal protection against CWR-induced injury.

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