Absorption border membrane

AC ADME ANS AUC BA/BE BBB BBM BBLM BCS BLM BSA CE CHO CMC CPC CPZ CTAB CV DA DOPC DPPC DPPH aminocoumarin absorption, distribution, metabolism, excretion anilinonaphthalenesulfonic acid area under the curve bioavailability-bioequivalence blood-brain barrier brush-border membrane brush-border lipid membrane biopharmaceutics classification system black lipid membrane bovine serum albumin capillary electrophoresis caroboxaldehyde critical micelle concentration centrifugal partition chromatography chlorpromazine cetyltrimethylammonium bromide cyclic votammetry dodecylcarboxylic acid dioleylphosphatidylcholine dipalmitoylphosphatidylcholine diphenylpicrylhydrazyl... 

The intestinal mucosal peptidases are distributed in the brush border and cytosol of the absorptive cell. There are, however, distinct differences between the brush border and cytosolic peptidases [75], The tetrapeptidase activity is associated exclusively with the brush border enzyme. Furthermore, brush border peptidases exhibit more activity against tripeptides than dipeptides, whereas the cytosolic enzymes show greater activity against dipeptides. Studies have demonstrated that more than 50% of dipeptidase activity was detected in the cytosol [76] and just 10% in the brush border membrane [77]. The brush border enzymes include... 

Ishizawa, T., et al. Mechanisms of intestinal absorption of the antibiotic, fosfomydn, in brush-border membrane vesicles in rabbits and humans./. Pharmacobiodyn. 1992, 25, 481-489. 

OATP2B1 (old name OATP-B) is expressed at brush-border membranes of intestinal epithelial cells [32], OATP2B1 exhibited pH-sensitive transport activities for various organic anions such as estrone-3-sulfate, dehydroepiandros-terone sulfate, taurocholic acid, pravastatin, and fexofenadine [33], However, further studies are needed to determine the specific physiological and pharmacokinetic contribution of OATP2B1 for intestinal absorption of these compounds. 

Figure 23.3 Drug transporters in the intestinal epithelial cells. PEPT1 is the most characterized transporter for intestinal drug absorption. The basolateral peptide transporter, which is not identified at the molecular level, also plays important roles. OATP-B, OCTN2 and MRP3 may be responsible for the intestinal absorption of some drugs. On the contrary, ABC transporters such as P-gp located at brush-border membranes mediated the efflux of drugs from intestinal epithelial cells, contributing to the low bioavailabihty of drugs such as the immunosuppressive agent, tacrolimus.

There have been sustained efforts in recent years to use the carrier systems of the brush-border membrane of intestinal mucosa to increase absorption of orally administered drugs [29] [30]. One system of particular interest is the intestinal peptide carrier (hPEPTl) whose physiological function is the absorption of di- and tripeptides and whose xenobiotic substrates include /3-lactam antibiotics, renin inhibitors, and angiotensin-converting enzyme (ACE) inhibitors [31]. 

Source and kinds of disaccharidases The final digestive processes occur at the mucosal lining of the small intestine. Several disaccharidases [for example, lactase (p-galactosidase), sucrase, maltase, and isomal-tase] produce monosaccharides (glucose, galactose, and fructose). These enzymes are secreted by and remain associated with the luminal side of the brush border membranes of intestinal mucosal cells. Absorption of the monosaccharides requires specific trans porters. 

Thomson, A.B.R. et al. (1993) Lipid absorption passing through the unstirred layers, brush-border membrane, and beyondCan. J. Physiol. Pharmacol., 71 531-555. 

Alcorn, C. J., R. J. Simpson, D. Leahy, and T. J. Peters. 109Cli.tro studies of intestinal drug absorption. Determination of partition and distribution coef dents with brush border membrane v iottBsm. Pharmacol. 42 2259-2264. 

Kellett, G.L. and P.A. Helliwell. 2000. The diffusive component of intestinal glucose absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane. Biochem J 350(Pt 1) 155. 

Hashimoto, T., et al. Improvement of intestinal absorption of peptides Adsorption of Bl-Phe monoglucosylated insulin to rat intestinal brush-border membrane vesicles. Eur J Pharm Biopharm 50 197. 

The layer of water adjacent to the absorptive membrane of the enterocyte is essentially unstirred. It can be visualized as a series of water lamellas, each progressively more stirred from the gut wall toward the lumen bulk. For BCS class 2 compounds the rate of permeation through the brush border is fast and the diffusion across the unstirred water layer (UWL) is the rate-limiting step in the permeation process. The thickness of the UWL in human jejunum was measured and found to be over 500 pm [3]. Owing to its thickness and hydrophilicity, the UWL may represent a major permeability barrier to the absorption of lipophilic compounds. The second mechanism by which the UWL functions act as a barrier to drug absorption is its effective surface area. The ratio of the surface area of the UWL to that of the underlying brush border membrane is at least 1 500 [4], i.e., this layer reduces the effective surface area available for the absorption of lipophilic compounds and hence impairs its bioavailability. 

Absorption of cholesterol in the small intestine contributes to maintaining whole-body cholesterol homeostasis, yet the mechanisms of absorption have not been completely defined. For many years it was believed that cholesterol, a normal component of cell membranes, simply diffused through the brush border membrane of enterocytes (Grundy, 1983 Westergaard and Dietschy, 1974). However, the discovery of specific transporters, receptors,... 

This article focuses on specific dietary components—whether naturally occurring or added as food ingredients—known to interfere with the mechanisms of cholesterol absorption. An overview of cholesterol absorption is provided and emphasizes the critical role of bile acids and micelle formation in solubilizing cholesterol for transport to the brush border membrane of enterocytes. Where applicable, information is also included about commercial food ingredients that are specifically used as cholesterollowering agents. 

The cells lining the lumen of the intestine are polarized, that is they have two distinct sides or domains which have different lipid and protein compositions. The apical or brush border membrane facing the lumen is highly folded into microvilli to increase the surface area available for the absorption of nutrients. The rest of the plasma membrane, the basolateral surface, is in contact with neighboring cells and the blood capillaries (Fig. 5). Movement between adjacent epithelial cells is prevented by the formation of tight junctions around the cells near the apical domain. Thus any nutrient molecules in the lumen of the intestine have to pass through the cytosol of the epithelial cell in order to enter the blood. 

OATP2B1 is ubiquitously expressed in the normal tissues (74,96). In comparison with human OATP1 family, OATP2B1 exhibited narrow substrate specificity (108). It is expressed in the sinusoidal membrane on the hepatocytes (108) and brush border membrane in the small intestine (109). OATP2B1 has been considered to mediate the intestinal absorption of fexofenadine and estrone sulfate (109,110). 

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