Mucus layer

V. cholerae is a gram-negative bacillus. Vibrios pass through the stomach to colonize the upper small intestine. Vibrios have filamentous protein extensions that attach to receptors on the intestinal mucosa, and their motility assists with penetration of the mucus layer.2 The cholera enterotoxin consists of two subunits, one of which (subunit A) is transported into the cells and causes an increase in cyclic AMP, which leads to a deluge of fluid into the small intestine.20 This large volume of fluid results in the watery diarrhea that is characteristic of cholera. The stools are an electrolyte-rich isotonic fluid, the loss of which results in blood volume depletion followed by low blood pressure and shock.2 Of note, the diarrheal fluid is highly infectious. 

Mucus layer (glycoprotein gel, 90% oligosaccharide, implicated in pH microclimate) Unstirred water layer... 

The glycocalyx and the mucus layer make up the structure of the unstirred water layer (UWL) [73]. The thickness of the UWL is estimated to be 30-100 pm in vivo, consistent with very efficient stirring effects [74]. In isolated tissue (in the absence of stirring), the mucus layer is 300-700 pm thick [73]. The pH in the unstirred water layer is 5.2-6.2, and might be regulated independently of the luminal pH (Section 2.3). The mucus layer may play a role in regulating the epithelial cell surface pH [73]. 

Shiau et al. [73] directly measured the microclimate pH, pHm, to be 5.2-6.7 in different sections of the intestine (very reproducible values in a given segment) covered with the normal mucus layer, as the luminal (bulk) pH, pH/, was maintained at 7.2. Good controls ruled out pH electrode artifacts. With the mucus layer washed off, pHm rose from 5.4 to 7.2. Values of pHfo as low as 3 and as high as 10 remarkably did not affect values of pHm. Glucose did not affect pHm when the microclimate was established. However, when the mucus layer had been washed off and pHm was allowed to rise to pHfo, the addition of 28 mM glucose caused the original low pHm to be reestablished after 5 min. Shiau et al. [73] hypothesized that the mucus layer was an ampholyte (of considerable pH buffer capacity) that created the pH acid microclimate. 

Said et al. [78] directly measured the acid microclimate on the surface of gastrointestinal tract (GIT) epithelial cells (intact with mucus layer) in rats. The pH on the apical (donor) side of the cells varied from 6.0 to 8.0, while the pH on the basolateral (acceptor) side was 7.4. Furthermore, the pH gradient between... 

Pontier, C. Pachot, J. Botham, R. Lefant, B. Amaud, R, HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption Role of mucus layer, J. Pharm. Sci. 90, 1608-1619 (2001). 

Lee, G.B. and Ogilvie, B.M. (1982) The intestinal mucus layer in Trichinella spiralis infected rats. In Strober, W., Hanson, L.A. and Sell, K.W. (eds) Recent Advances in Mucosal Immunity. Raven Press, New York, p. 319. 

MTX have also been evaluated as models with modified paracellular permeability and the additional presence of a mucus layer [77, 79, 81],... 

Wikman, A., Karlsson, J., Carlstedt, I., Artursson, P., A drug absorption model based on the mucus layer producing human intestinal goblet cell line HT29-H, Pharm. Res. 1993, 30, 843-852. 

There is also a gradient from the low luminal pH through the mucus layer, under which gastric bicarbonate secretion maintains neutral conditions. Mechanically, this is explained by the acid secretion occurring like small finger-like ejections penetrating the thick gel-like mucus layer into the gastric lumen [27]. 

In the present review the gastric lumen is confined to the habitat above the mucus layer, for which the pH of fasting gastric juice is the major defense mechanism against bacterial colonization. This defense mechanism is henceforth denoted the gastric acid barrier. 

Schultsz C, van den Berg FM, ten Kate FW, Tytgat GN, Dankert J The intestinal mucus layer from patients with inflammatory bowel disease harbours numbers of bacteria compared with controls. Gastroenterology 1999 117 1089-1097. 

Donnan potential a voltage arising from the passive uneven distribution of diffusible ions, usually across a cell membrane, or between a mucus layer and simple saline solution. 

In addition to the intercellular lipids of the buccal mucosa, there appear to be other barriers which may reduce the ability of an exogenous compound to permeate the buccal mucosa. These include the salivary film and mucus layer, the basement membrane, and a metabolic barrier. 

The function of the mucosal pellicle is to serve as a barrier between the oral epithelial surface and the external environment, and so it may also act as a barrier to drug delivery. However, there are limited studies assessing the role of the mucus layer in buccal permeability. In one study, treatment of the oral mucosa with anticholinergic agents resulted in an increased permeability of certain compounds, and it was suggested that the reduced salivary flow may have been responsible for the reduced barrier properties of the tissue [113]. In... 

Lack of mucus secreting cells resulting in absence of a mucus layer... 

Similar to the PAMPA and the Caco-2 models, the experimental pH of the buffer solution can be changed in the Ussing chambers model. However, it seems that the impact of changing the pH of the mucosal (= apical) buffer solution is lower than for the other two systems [82], This is probably due to the presence of the mucus layer retaining the microclimate pH regardless of the luminal pH using the Ussing chambers technique [82],... 

Karlsson J, Wikman A, Artursson P (1993) The mucus layer as a barrier to drug absorption in monolayers of human intestinal epithelial HT29-H goblet cells. Int JPharm 99 209-218. 

In the gut sac technique, animal intestinal segments are divided into 2-cm sacs by tying off each end. The sacs, with or without musculature, can be everted or not to measure directional drug transport into or out of the sacs. The sacs are placed in a vessel containing an oxygenated buffer and transport is measured with normalization for the sac size. The intestinal gut sac method is a relatively fast and inexpensive technique for measuring permeability that includes all intestinal cell types and mucus layer. 

Although the mucus layer acts as a barrier to some invading pathogens, it also supports the growth and maintenance of a number of commensal bacteria in the GIT. It acts as an initial binding site, a source of nutrients for growth, and is a niche where these bacteria can replicate and potentially compete with other newly introduced bacteria (Laux et ah, 2005). Therefore, tissues that produce mucus have the potential to provide the host... 

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