Acid Transport through Gastric Mucus

Phillipson, Mia

doi:10.3109/2000-1967-106

Cited by 12 publications

(6 citation statements)

References 57 publications

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“…The epithelial level consists of intercellular tight junctions and proton and bicarbonate transport systems. The postepithelial level consists mainly of an effective blood flow and the gastrointestinal autonomic nervous system [37]. Gastric mucosal damage can be induced by aggressive factors like hydrochloric acid, pepsin, leukotrienes, free radicals, nonsteroidal anti-inflammatory drugs (NSAIDs), ischemia, dysmotility, ethanol, nicotine, and stress [38].…”

Section: Introductionmentioning

confidence: 99%

Gastric Antiulcerogenic and Hypokinetic Activities ofTerminalia fagifoliaMart. & Zucc. (Combretaceae)

Nunes

Martins

Oliveira

et al. 2014

BioMed Research International

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The acute toxicity, the antioxidant activity, and the pharmacological activity on the gastrointestinal tract of rodents of the ethanolic extract (TFEE) from the bark of Terminalia fagifolia Mart. & Zucc. (Combretaceae) and of its aqueous (TFAqF), hydroalcoholic (TFHAF), and hexanic (TFHEXF) partition fractions have been evaluated. TFEE presented low acute toxicity, antioxidant, and antiulcerogenic activity against ethanol-induced ulcers, which was partially blocked by pretreatment with L-NAME and indomethacin. It reduced the total acidity and raised the pH of gastric secretion. Additionally, TFEE delayed gastric emptying and slightly inhibited the small intestinal transit and also presented a weakly antidiarrheal activity. The antiulcerogenic and antioxidant activity were also detected in TFAqF and TFHAF but not in TFHEXF. The antisecretory and gastroprotective activity of TFEE partially involve the nitric oxide and prostaglandin participation. Nevertheless, TFEE, TFAqF, and TFHAF drastically reduced the mucus layer adhered to the gastric wall of rats treated with ethanol or indomethacin. Complementary studies are required in order to clarify the paradox of the presence of a gastroprotector activity in this plant that, at the same time, reduces the mucus layer adhered to the gastric wall.

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Section: Introductionmentioning

confidence: 99%

Gastric Antiulcerogenic and Hypokinetic Activities ofTerminalia fagifoliaMart. & Zucc. (Combretaceae)

Nunes

Martins

Oliveira

et al. 2014

BioMed Research International

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“…One criticism that has been leveled at the mechanism proposed by Schreiber, et. al (see [22]) is that these numbers appear to be too low to account for the larger fluxes of hydrogen that may be secreted by either the human [6] or guinea pig stomach [5]. However, the fluxes implied by [25] are not completely incompatible with observed hydrogen fluxes.…”

mentioning

confidence: 99%

A physics-based model for maintenance of the pH gradient in the gastric mucus layer

Lewis

Keener

Fogelson

2017

American Journal of Physiology-Gastrointestinal and Liver Physi

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It is generally accepted that the gastric mucus layer provides a protective barrier between the lumen and the mucosa, shielding the mucosa from acid and digestive enzymes and preventing autodigestion of the stomach epithelium. However, the precise mechanisms that contribute to this protective function are still up for debate. In particular, it is not clear what physical processes are responsible for transporting hydrogen protons, secreted within the gastric pits, across the mucus layer to the lumen without acidifying the environment adjacent to the epithelium. One hypothesis is that hydrogen may be bound to the mucin polymers themselves as they are convected away from the mucosal surface and eventually degraded in the stomach lumen. It is also not clear what mechanisms prevent hydrogen from diffusing back toward the mucosal surface, thereby lowering the local pH. In this work we investigate a physics-based model of ion transport within the mucosal layer based on a Nernst-Planck-like equation. Analysis of this model shows that the mechanism of transporting protons bound to the mucus gel is capable of reproducing the trans-mucus pH gradients reported in the literature. Furthermore, when coupled with ion exchange at the epithelial surface, our analysis shows that bicarbonate secretion alone is capable of neutralizing the epithelial pH, even in the face of enormous diffusive gradients of hydrogen. Maintenance of the pH gradient is found to be robust to a wide array of perturbations in both physiological and phenomenological model parameters, suggesting a robust physiological control mechanism. This work combines modeling techniques based on physical principles, as well as novel numerical simulations to test the plausibility of one hypothesized mechanism for proton transport across the gastric mucus layer. Results show that this mechanism is able to maintain the extreme pH gradient seen in in vivo experiments and suggests a highly robust regulation mechanism to maintain this gradient in the face of dynamic lumen composition.

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“…HCO 3 ) secretion into the lumen could be measured when acid secretion was inhibited (Flemströ m 1977, Garner & Flemströ m 1978, Flemströ m & Garner 1982), but also, in an indirect way, in an acid-secreting stomach (Altamirano 1963, Garner & Flemströ m 1978, Feldman & Barnett 1985. However, recent experiments leave no doubt that the luminal fluid directly above gastric surface cells becomes more alkaline when the stomach secretes acid (Phillipson 2004), and that this function is impaired in Helicobacter-infected mice (Henriksnas et al 2006). However, recent experiments leave no doubt that the luminal fluid directly above gastric surface cells becomes more alkaline when the stomach secretes acid (Phillipson 2004), and that this function is impaired in Helicobacter-infected mice (Henriksnas et al 2006).…”

Section: Hco 3 ) Secretion In the Stomachmentioning

confidence: 99%

“…Its existence, protective role for the gastric epithelium and involved transporters were controversially discussed for a long time (Wallace 1989). However, recent experiments leave no doubt that the luminal fluid directly above gastric surface cells becomes more alkaline when the stomach secretes acid (Phillipson 2004), and that this function is impaired in Helicobacter-infected mice (Henriksnas et al 2006). In addition, Debellis et al (1998) have measured HCO 3 ) secretion in the depths of the gastric glands in frog stomach that could be stimulated by cholinergic agents and shut off by histamine, and seemed to involve HCO 3 ) import into the secreting cells via NBC.…”

Section: Hco 3 ) Secretion In the Stomachmentioning

confidence: 99%

“…As the acid secretory rates in the stomach were much higher than those for HCO 3 ) (Holton & Spencer 1976, Flemströ m 1977, Sjö strand et al 1977, Garner & Flemströ m 1978, 1978 and as gastric and duodenal mucin gels were found to provide no major barrier to H + ion permeation , this concept was much disputed (Wallace 1989). It nevertheless stood the test of time, or, more correctly phrased, was proven correct by even the most advanced experimental techniques (Phillipson 2004, Sjö blom et al 2009). While others still strove to delineate the role of HCO 3 ) secretion in the complex scenario of gastroduodenal mucosal protection, Gunnar and his group went far beyond the gastroduodenal epithelium and demonstrated that our central nervous system elaborately controls the output of HCO 3 ) into the duodenal lumen (Flemströ m & Sjö blom 2005).…”

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confidence: 99%

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Recent advances in the molecular and functional characterization of acid/base and electrolyte transporters in the basolateral membranes of gastric and duodenal epithelial cells

et al. 2010

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All segments of the gastrointestinal tract are comprised of an elaborately folded epithelium that expresses a variety of cell types and performs multiple secretory and absorptive functions. While the apical membrane expresses the electrolyte transporters that secrete or absorb electrolytes and water, basolateral transporters regulate the secretory or absorptive rates. During gastric acid formation, Cl⁻/HCO₃⁻ and Na(+) /H(+) exchange and other transporters secure Cl⁻ re-supply as well as pH and volume regulation. Gastric surface cells utilize ion transporters to secrete HCO₃⁻, maintain pH(i) during a luminal acid load and repair damaged surface areas during the process of epithelial restitution. Na(+)/H(+) exchange and Na(+)/HCO₃⁻ cotransport serve basolateral acid/base import for gastroduodenal HCO₃⁻ secretion. The gastric and duodenal epithelium also absorbs salt and water. Recent molecular information on novel ion transporters expressed in the gastric and duodenal epithelium has exploded; however, a function has not been found yet for all transporters. The purpose of this review is to summarize current knowledge on the molecular identity and cellular function of basolateral ion transporters in the gastric and duodenal epithelium.

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Acid Transport through Gastric Mucus

Cited by 12 publications

References 57 publications

Gastric Antiulcerogenic and Hypokinetic Activities ofTerminalia fagifoliaMart. & Zucc. (Combretaceae)

Gastric Antiulcerogenic and Hypokinetic Activities ofTerminalia fagifoliaMart. & Zucc. (Combretaceae)

A physics-based model for maintenance of the pH gradient in the gastric mucus layer

Recent advances in the molecular and functional characterization of acid/base and electrolyte transporters in the basolateral membranes of gastric and duodenal epithelial cells

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