Significance of the goblet-cell mucin layer, the outermost luminal barrier to passage through the gut wall

Nimmerfall, Fritz; Rosenthaler, J.

doi:10.1016/0006-291x(80)91328-5

Cited by 80 publications

(24 citation statements)

References 14 publications

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“…In most hydrophobic drugs, UWL permeation would be the ratelimiting step in their intestinal absorption. 19,20 UWL consists of a mucus layer composed mainly of water and glycoproteins, which form a highly viscous gel-like network. It has been Effects of NOC7 or DTT on the apparent permeability coefficients (P app ) of griseofulvin in rat duodenum.…”

Section: Contribution Of Mucus Layer To the Absorption-enhancing Effementioning

confidence: 99%

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

Kishimoto

Miyazaki

Takizawa

et al. 2016

Journal of Pharmaceutical Sciences

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Nitric oxide (NO), an endogenous gas that plays a versatile role in the physiological system, has the ability to increase the intestinal absorption of water-soluble compounds through the paracellular route. However, it remains unclear whether NO can enhance the absorption of hydrophobic drugs through the transcellular route. In this study, we examined the absorption-enhancing effect of NO on intestinal permeability of hydrophobic drugs in rat intestine. The pretreatment of rat gastrointestinal sacs with NOC7, a NO-releasing reagent, significantly increased the permeation of griseofulvin from mucosa to serosa in the sacs prepared from the duodenum, but not in those prepared from the other regions such as jejunum, ileum, and colon. The absorption-enhancing effect of NOC7 on the duodenal permeation varied depending on the hydrophobicity of the drugs used. Furthermore, NOC7 treatment was found to be apparently ineffective on the griseofulvin permeation in the duodenum pretreated with dithiothreitol (DTT) that was used as a mucus remover, even though the permeation was increased by pretreatment with DTT alone. These results suggest that NO increases the absorption of hydrophobic drugs through the transcellular route in the duodenum by modulating the mucus layer function.

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Section: Contribution Of Mucus Layer To the Absorption-enhancing Effementioning

confidence: 99%

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

Kishimoto

Miyazaki

Takizawa

et al. 2016

Journal of Pharmaceutical Sciences

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“…Such an effect of Con A could be correlated to what Freed [11] named 'mucotractive' effect [12,21]. Freed [11] suggest that the mucus thus released could form an additional barrier to absorption of larger molecules [22] and thereby reduce the transmural passage. In ac cordance, we have recently found that mucolytic agents increase the permeation of FITC-D3 in rat in testine [28].…”

Section: Discussionmentioning

confidence: 99%

“…The effects of lectins may be the result of either a reduced cyto plasm-membrane flow, or of interference with the normal cytoskeleton-plasma-membrane association [20]. The binding of Con A to the mucosal membrane could thus result in both an additional permeability barrier [22] due to mucus release [11,16] and a pertur bation of the brush border membrane ( fig. 5) [20].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Concanavalin A and Wheat Germ Agglutinin on the Ultrastructure and Permeability of Rat Intestine

Sjölander¹,

Magnusson²,

Latkovic³

1984

Int Arch Allergy Immunol

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Sprague-Dawley rats were exposed to lectins, either concanavalin A (Con A) or wheat germ agglutinin (WGA). The lectins were instilled into a ligated segment of the distal small intestine together with permeability markers, fluoresceinated dextran (MW 3,000) or a mixture of differently sized polyethylene glycols (MW 400, 600 and 1,000). WGA-treated rats showed a decreased permeability to small molecules (MW <600) of polyethylene glycol but an increase for a larger dextran molecule (MW 3,000). These effects as well as the morphological findings might mimic the situation in patients with food allergy or celiac disease. Con A-treated rats had decreased intestinal permeability to the larger dextran molecules (MW 3,000), whereas the passage of small molecules was unaffected and the ultrastructural effects were minute. The Con A-induced changes could result from a mucotractive effect, associated with a low-grade gut allergy. These observations suggest that lectins can affect both the ultrastructure and the permeability of the intestine, in a way assumed to mimic allergic reactions to food constituents.

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“…Depth of the unstirred water layer is largely determined by the length of membrane associated mucin extending from the microvilli apex or referred to as glycocalyx (Atuma et al, 2001). This co-operative effort between membrane associated mucin (glycocalyx) and secretory mucin from goblet cells results in what has been considered as the primary and purposeful barrier to formal absorption (Nimmerfall and Rosenthaler, 1980;Smithson et al, 1981;Smithson, 1983) (Fig. 4).…”

Section: Figmentioning

confidence: 99%

Gastric digestion of protein through pancreozyme action optimizes intestinal forms for absorption, mucin formation and villus integrity

Moran

2016

Animal Feed Science and Technology

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a b s t r a c tRecovery of dietary protein proceeds through two phases of digestion before suitable forms exist for absorption. The first phase engages the gastric system where low pH weakens overall structures allowing pepsin to disrupt hydrophobic bonding and enhance aqueous compatibility. Secondly, trypsin, chymotrypsin and elastase proteolysis in conjunction with carboxypeptidases A and B cooperate to form a mixture of free amino acids and peptides that progressively arise in the small intestinal lumen. Free amino acids are dominated by the aromatic, aliphatic and basic ones while resulting peptides largely involve the nonessentials.Motility convectively transfers digestion products to the unstirred water layer of the upper villus where filtration limits entry to low molecular weight solutes that can be further digested by underlying enzymes to optimize membrane absorption. Mucin oligosaccharides are credited for creating a microenvironment having reduced pH's ∼5.5-6.0 that favors enzymes finalizing digestion as well as absorption of two type peptides. This pH is speculated to optimize peptide forms having either a zwitterion-like charge for proton gradient transfer or be non-dissociated and passively diffused. A high frequency of peptides having either glycine or proline can be rationalized as providing particularly favorable electronic terms for peptide absorption by either approach while being non-competitive.The upper villus has first access to absorbed products where goblet cells assure continuance of mucin and continuity of the unstirred water layer. Glutamine is their dominant nutrient for synthesis of mucin oligosaccharides while also providing glutamic acid for either formation of its associated protein or is consumed for energy. Dietary cystine and threonine are frequently limiting, and their assurance is necessary for the mucin core while ready availability of glycine and/or serine together with proline also foster mucin formation. Unused absorbed products descend the villus in venules adjacent to the surface and provide nutrition as well as information about the lumen for adaptation of replacement cells. Sustaining the villus with absorbed nutrients takes priority for continuation of operational efficiency before their entry into the portal system and subsequent body use.

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Significance of the goblet-cell mucin layer, the outermost luminal barrier to passage through the gut wall

Cited by 80 publications

References 14 publications

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

Absorption-Enhancing Effect of Nitric Oxide on the Absorption of Hydrophobic Drugs in Rat Duodenum

The Effect of Concanavalin A and Wheat Germ Agglutinin on the Ultrastructure and Permeability of Rat Intestine

Gastric digestion of protein through pancreozyme action optimizes intestinal forms for absorption, mucin formation and villus integrity

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