Intestinal absorption Brush-Border transporters

Glucose and galactose enter the absorptive cells by way of secondary active transport. Cotransport carrier molecules associated with the disaccharidases in the brush border transport the monosaccharide and a Na+ ion from the lumen of the small intestine into the absorptive cell. This process is referred to as "secondary" because the cotransport carriers operate passively and do not require energy. However, they do require a concentration gradient for the transport of Na+ ions into the cell. This gradient is established by the active transport of Na+ ions out of the absorptive cell at the basolateral surface. Fructose enters the absorptive cells by way of facilitated diffusion. All monosaccharide molecules exit the absorptive cells by way of facilitated diffusion and enter the blood capillaries. 

Some Brush-Border Transporters Involved in Intestinal Absorption Processes, Pertinent to Gl Drug Absorption... 

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.

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

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,... 

FIG. 1 Digestion and absorption of proteins in the small intestine. (1) Brush-border peptidases, (2) brush-border amino acid transport systems, (3) brush-border peptide transport systems, (4) cytoplasmic peptidases, (5) basolateral amino acid transport systems, (6) basolateral peptide transport systems. 

Q1 The mucosa is a mucous membrane which forms the innermost layer of the intestine. In the small intestine the mucosal surface area is increased greatly by folds and by villi, finger-like projections containing a core with a lymph capillary (lacteal) and blood vessels. Villi are covered by absorptive columnar epithelial cells whose luminal surface is further increased by microvilli (brush border) on which digestive enzymes and transport mechanisms for inorganic ions are located. 

The mucosa of the small intestine has an enormous surface area because of the presence of villi. Villi are covered by absorptive columnar epithelial cells whose surface is further increased by microvilli (brush border), on which carbohydrate and peptide digestive enzymes and transport processes involved in absorption are situated. Pits between the villi contain undifferentiated cells which move up the villi, mature, function for a few days and are shed into the lumen of the gut. 

Studies of zinc transport with isolated, vascularly perfused rat intestine and brush border vescicles fail to support a role for a unique binding ligand in zinc absorption. 

The studies reported here using the isolated, vascularly perfused rat intestine system and isolated brush border membrane vesicles fail to support a role for a specific zinc-binding ligand involved in zinc uptake in the rat. Rather, the extent of zinc uptake involves the interaction of several phenomena, including both extracellular and intracellular reactions. It appears that the major pathway of zinc uptake under normal dietary conditions involves the transfer of zinc from various dietary components to a carrier mediated transport system at the brush border membrane. The net absorption of zinc from the lumen could involve a competition between various dietary components, zinc binding ligands and the membrane carrier for zinc. Thus, in some cases, those compounds in the lumen with a higher affinity for zinc than the membrane component will be less likely to permit transfer of zinc to the carrier, while compounds with a lower affinity for zinc will increase the amount of zinc made... 

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