Gastroduodenal Mucosal Defense

Montrose, Marshall H.

doi:10.1016/b978-012088394-3/50053-2

Cited by 17 publications

(33 citation statements)

References 293 publications

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“…We propose that this barrier might function as one of the secondary defensive barriers when the primary barrier of the epithelium has been broken in such a clinical disorder as inflammatory bowel disease (1,5). However, several issues need to be addressed before confirming the significance of our findings.…”

Section: Discussionmentioning

confidence: 58%

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In Vitro Diffusion Barriers of the Mouse Jejunum in Ussing Chambers

Inagaki-Tachibana

Natori

Hayashi

et al. 2008

J Nutr Sci Vitaminol

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Summary Epithelial cells and their intercellular junctions play a primary role in the intestinal mucosal diffusion barrier to the invasion of noxious agents. Our previous study has shown that the mouse jejunum, when incubated in Ussing chambers for 4 h, exhibited morphological deterioration of the villi with denudation of the epithelia while it retained cAMP-induced potential difference (PD), suggesting that some subepithelial tissues had taken part in the barrier functions when the primary epithelial barrier on the villous surface was broken. To further characterize the barrier function of the jejunum in Ussing chambers, we measured the unidirectional lucifer yellow flux ( J LY ), which represents the permeation of a medium-sized anion, the transmural electrical conductance ( G t ), which reflects the permeation of electrolytes, mainly NaCl, and forskolin-induced PD. The values of J LY , G t and forskolin-induced PD were not affected by removing the muscularis propria, suggesting that this tissue did not substantially contribute to the barrier. In addition, the values of J LY , G t and forskolin-induced PD were not correlated with the degree of denudation of epithelial cells on the mucosal surface, supporting the notion that the main barrier function is constituted by the subepithelial tissues rather than the epithelium. Loosening the tissue (thereby approximating the free diffusion condition) by removing Ca 2 ϩ from the bathing solution increased both J LY and G t , with the former being larger than the latter. In conclusion, the mucosa propria and/or the submucosa constitute a diffusion barrier that restricted the permeation of lucifer yellow more tightly than NaCl in the injured jejunum incubated in Ussing chambers.

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Section: Discussionmentioning

confidence: 58%

“…3). It is generally agreed that the tight junction between epithelial cells is the major, if not sole, gate restricting the diffusion of electrolytes and small water-soluble molecules (1,5,6). Therefore, the "intact" epithelium on the shortened villus area may not retain the normal tight-junction structure and barrier functions.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Diffusion Barriers of the Mouse Jejunum in Ussing Chambers

Inagaki-Tachibana

Natori

Hayashi

et al. 2008

J Nutr Sci Vitaminol

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“…The secretion of HCO 3 Ϫ from the surface epithelium is one of the mucosal defensive mechanisms and plays an important role in protecting the gastroduodenal mucosa against acid (Flemström and Garner, 1982;Flemström, 1987;Allen et al, 1993;Montrose et al, 2005). This secretion is controlled by various neurohumoral factors as well as luminal acid (Flemström, 1987;Takeuchi et al, 1991), with endogenous PGs and NO being particularly important in its local regulation (Heylings et al, 1984;Takeuchi et al, 1999;Sugamoto et al, 2001;Aihara et al, 2005b).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms that govern HCO 3 Ϫ secretion involve neurohumoral factors and luminal acid (Flemström and Garner, 1982;Takeuchi et al, 1991;Montrose et al, 2005); yet, both endogenous prostaglandins (PGs) and nitric oxide (NO) play a particularly important role in the local control of this secretion (Heylings et al, 1984;Takeuchi et al, 1986;Sugamoto et al, 2001, Aihara et al, 2005b. The stimulatory effect of PGE 2 on HCO 3 Ϫ secretion in the stomach is known to be mediated by the activation of EP1 receptors and coupled intracellularly with Ca 2ϩ (Takeuchi et al, 1997b.…”

Section: The Secretion Of Hcomentioning

confidence: 99%

Phosphodiesterase Isozymes Involved in Regulation of Secretion in Isolated Mouse Stomach in Vitro

Kita

Takahashi²,

Ohashi³

et al. 2008

J Pharmacol Exp Ther

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(Ϯ)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide](NOR-3), a nitric-oxide (NO) donor, is known to increase HCO 3 Ϫ secretion in rat stomachs, intracellularly mediated by cGMP; yet, there is no information about the phosphodiesterase (PDE) isozyme involved in this process. We examined the effects of various isozyme-selective PDE inhibitors on the secretion of HCO 3 Ϫ in the mouse stomach in vitro and the type(s) of PDE isozymes involved in the response to NO. The gastric mucosa of DDY mice was stripped of the muscle layer and mounted on an Ussing chamber. HCO 3 Ϫ secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. NOR-3, 8-bromoguanosine 3Ј,5Ј-cyclic monophosphate (8-Br-cGMP), and various PDE inhibitors were added to the serosal side. Vinpocetine (PDE1 inhibitor) or zaprinast (PDE5 inhibitor) was also added serosally 30 min before NOR-3 or 8-Br-cGMP. Both NOR-3 and 8-Br-cGMP stimulated HCO 3 Ϫ secretion in a dosedependent manner, and the response to NOR-3 was significantly inhibited by methylene blue. Likewise, the secretion induced by NOR-3 or 8-Br-cGMP was significantly attenuated by 6-((2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo(2.2.2)octan-2-yl)-5Z-hexenoic acid (ONO-8711), the PGE receptor (EP)1 antagonist, as well as indomethacin and potentiated by both vinpocetine and zaprinast at doses that had no effect by themselves on the basal secretion, whereas other subtype-selective PDE inhibitors had no effect. NOR-3 increased the mucosal PGE 2 content in a methylene blueinhibitable manner. These results suggest that NO stimulates gastric HCO 3 Ϫ secretion mediated intracellularly by cGMP and modified by both PDE1 and PDE5, and this response is finally mediated by endogenous PGE 2 via the activation of EP1 receptors.

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“…The physiological basis of duodenal mucosal protection involves several factors, and the protection is categorized into three levels of defence: pre-epithelial, epithelial and subepithelial (Allen et al 1993, Flemströ m 1994, Flemströ m & Isenberg 2001, Allen & Flemströ m 2005, Montrose et al 2006. The physiological basis of duodenal mucosal protection involves several factors, and the protection is categorized into three levels of defence: pre-epithelial, epithelial and subepithelial (Allen et al 1993, Flemströ m 1994, Flemströ m & Isenberg 2001, Allen & Flemströ m 2005, Montrose et al 2006.…”

Section: Duodenal Mucosal Defencementioning

confidence: 99%

Duodenal epithelial sensing of luminal acid: role of carbonic anhydrases

Sjöblom

2010

Acta Physiologica

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Sensing the luminal contents is a prerequisite to activate appropriate gastrointestinal functions. A major task of the duodenal epithelium is to resist the repeated challenges of hydrochloric acid expelled from the stomach. Although extensive research in this field, the complete mechanisms providing this defence remain to be revealed. The duodenal epithelium exports bicarbonate into a submillimetre-thick mucus gel on top of the mucosal surface. Despite the very low pH of the luminal contents, the duodenal mucus-bicarbonate barrier provides a means of maintaining a virtually neutral pH at the epithelial surface. Instead of pH, CO₂ generated by the mixing of acid and bicarbonate at levels not found elsewhere in the body serves as the mediator for sensing the luminal acid. Carbonic anhydrases (CAs) catalyse the reversible hydration of CO₂ and are heavily expressed in the duodenal segment. Accumulating data support the key function of CAs in sensing luminal acid and CO₂. Recent advances demonstrate that the presence of CA II in upper villus plays a crucial role in enterocyte intracellular acidification preceding the secretory increase in response to luminal acid. However, CAs only have a minor role in the bicarbonate supply destined for duodenal bicarbonate secretion into the lumen. The purpose of this review is to summarize the current knowledge of how intraluminal acid is sensed by the duodenal mucosa, with a focus on the role of CAs.

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Gastroduodenal Mucosal Defense

Cited by 17 publications

References 293 publications

In Vitro Diffusion Barriers of the Mouse Jejunum in Ussing Chambers

In Vitro Diffusion Barriers of the Mouse Jejunum in Ussing Chambers

Phosphodiesterase Isozymes Involved in Regulation of Secretion in Isolated Mouse Stomach in Vitro

Duodenal epithelial sensing of luminal acid: role of carbonic anhydrases

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