Mucins intestinal

Figure 5.28 LC-electrospray-MS total ion chromatogram of sulfated oligosaccharides from mucins purified from the porcine large intestine, where the annotations indicate the molecular ions observed from each component. Reprinted with permission from Thoms-son, K. A., Karlsson, H. and Hansson, G. C., Anal. Chem., 72, 4543-4549 (2000). Copyright (2000) American Chemical Society.

The genes encoding the polypeptide backbones of a number of mucins derived from various tissues (eg, pancreas, small intestine, trachea and bronchi, stomach, and salivary glands) have been cloned and sequenced. These studies have revealed new information about the polypeptide backbones of mucins (size of tandem repeats, potential sites of N-glycosylation, etc) and ultimately should reveal aspects of their genetic control. Some important properties of mucins are summarized in Table 47-8. 

Mucin, a viscous mucopolysaccharide that lines and protects the intestinal epithelium, has been thought to bind certain drugs nonspecifically (e.g., quarternary ammonium compounds) and thereby prevent or reduce absorption. This behavior may partially account for the erratic and incomplete absorption of such charged... 

JJ Niibuchi, Y Aramaki, S Tsuchiya. Binding of antibiotics to rat intestinal mucin. Int J Pharm 30 181-187, 1986. 

Ishikawa, N., Horii, Y. and Nawa, Y. (1993) Immune mediated alteration of the terminal sugars of goblet cell mucins in the small intestine of Nippostrongylus brasiliensis infected rats. Immunology 78, 303-307. 

Increased numbers of goblet cells (GCs) and qualitative changes in mucus secretions are coincident with infection with a number of nematode parasites and it has been proposed that mucin proteins mediate this response by enveloping the parasites and/or interrupting attachment (Nawa et al., 1994). However, the role of GCs and mucus in the generation of a protective response versus its role in resolving intestinal inflammation following infection with GI nematode parasites remains unresolved. 

Mucins are also thought to act in cooperation with trefoil proteins in the protection and repair of the epithelium (Kindon et al., 1995). Trefoil factors are expressed along the GI tract and increased levels are noted near sites of inflammation and ulcerative lesions (Babyatsky et al., 1996). Furthermore, it has been demonstrated that mouse intestinal trefoil factor may play a role in the alteration of the physicochemical nature of GC mucins during N. brasiliensis infection (Tomita et al., 1995). Perhaps in GI nematode parasite infection mucins are not aiding in the host s protective expulsion of the parasite, but rather are functioning in the repair of the damaged intestinal epithelium. 

Kindon, H., Pothoulakis, C., Thim, L., Lynch-Devaney, K. and Podolsky, D.K. (1995) Trefoil peptide protection of intestinal epithelial barrier function cooperative interaction with mucin glycoprotein. Gastroenterobgy 109, 516-523. 

Lindahl, M., and Carlstedt, I. (1990). Binding of K99 fimbriae of enterotoxigenic Escherichia coli to pig small intestinal mucin glycopeptides. J. Gen. Microbiol. 136,1609-1614. 

Mantle, M., and Husar, S. D. (1994). Binding of Yersinia enterocolitica to purified, native small intestinal mucins from rabbits and humans involves interactions with the mucin carbohydrate moiety. Infect. Immun. 62,1219-1227. 

Smith, C. J., Kaper, J. B., and Mack, D. R. (1995). Intestinal mucin inhibits adhesion of human enteropathogenic Escherichia coli to HEp-2 cells. J. Pediatr. Gastroenterol. Nutr. 21,269-276. 

Sylvester, F., Philpott, D., Gold, B., Lastovica, A., and Forstner, J. (1996). Adherence to lipids and intestinal mucin by a recently recognized human pathogen, Campylobacter upsaliensis. Infect. Immun. 64,4060 066. 

Vimal, D. B., Khullar, M., Gupta, S., and Ganguly, N. K. (2000). Intestinal mucins The binding sites for Salmonella typhimerium. Mol. Cell. Biochem. 204,107-117. 

Karlsson, N.G. Karlsson, H. Hansson, G.C. Sulfated Mucin Oligosaccharides From Porcine Small Intestine Analyzed by Four-Sector Tandem Mass Spectrometry. J. Mass Spectrom. 1996, 31. 560-572. 

Another possible mechanism of potentiator action, the barrier disruption hypothesis, has received considerable attention. This theory of potentiator action, first proposed by Parrot and Nicot (24), suggests that the potentiators may interfere with the protective actions of intestinal mucin. Mucin is known to bind histamine in vitro (53), and Parrot and Nicot ( ) suggested that this binding was essential to prevent passage of histamine across the intestinal wall. Potentiators such as putrescine and cadaverine... 

Later, Chu and Bjeldanes (53) showed that the binding histamine to mucin could be inhibited in vitro by spermine, spermidine, putrescine, cadaverine, and a basic extract of tuna. The inhibition required relatively high amine concentrations, and the concentrated tuna extract exerted only a 23% inhibition of binding ( ). Each mole of intestinal mucin can bind 2.5 moles of histamine (53). 

Histochemical demonstration of most of the O-acetylated sialic acids is possible because substituents on the side chain of Neu hinder periodate oxidation of this part of the molecule to an extent dependent on the number and position of the O-acetyl groups already mentioned. Correspondingly, removal of these ester groups by alkaline treatment (0.5% KOH in 70% ethanol91) may increase the staining reaction of a sialic acid. For example, the presence of O-acylated sialic acids has been demonstrated in colonic, epithelial mucin of man and various mammals (summarized in Ref. 91), in healthy and diseased, human small-intestine,188-190 in bovine submandibular gland,182 in mouse and rat erythrocyte-membranes,191 and in human lymphocytes.192... 

Rat, small-intestinal mucosa Porcine, submaxillary mucin o-Fue-(l— 2) none 51... 

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