Membrane transport proteins intestinal peptide transporter

As mentioned above, the rectal route is very attractive for systemic delivery of peptide and protein drugs, but rectal administration of peptides often results in very low bioavailability due to not only poor membrane penetration characteristics (transport barrier) but also due to hydrolysis of peptides by digestive enzymes of the GI tract (enzymatic barrier). Of these two barriers, the latter is of greater importance for certain unstable small peptides, as these peptides, unless they have been degraded by various proteases, can be transported across the intestinal membrane. Therefore, the use of protease inhibitors is one of the most promising approaches to overcome the delivery problems of these peptides and proteins. Many compounds have been used as protease inhibitors for improving the stability of various peptides and proteins. These include aprotinin, trypsin inhibitors, bacitracin, puromycin, bestatin, and bile salts such as NaCC and are frequently used with absorption enhancers for improvement in rectal absorption. 

The transport of some solutes across membranes does not resemble diffusion and suggests a temporary, specific interaction of the solute with some component (protein) of the membrane characterized as carrier, e.g., the small-peptide carrier of the intestinal epithelium. The rate of transport increases in proportion to concentration only when this is small, and it attains a maximal rate that cannot be exceeded even with a large further increase in concentration. The kinetics of carrier-mediated transport is theoretically treated by considering carrier-solute... 

Amino acids, dipeptides, and some tripeptides are transported from the lumen of the intestine through the membrane of the brush border of the mucosal cells and into the cytoplasm, where the peptides are hydrolyzed to amino acids. Transport of peptides and amino acids is active and analogous to glucose transport i.e., they are transported, together with Na+, across the gut-cell membrane by specific transport proteins called Na+ symports. Between the gut lumen and the cytoplasm of the cell there is a concentration gradient of Na+ that is maintained by Na+/K+ ATPase at the base of the cell adjacent to the blood capillaries this Na+/K ATPase pumps Na+ from the cell into the blood. 

After the break down of proteins by proteolytic enzymes, the pancreas, and brush border peptidases, the di- and trip-eptides are absorbed through the epithelial cell membrane. Many studies have shown that intact di- and tripeptides are absorbed across the epithelial cell membrane by active transport via specific carrier systems. The absorption process is mediated by the hydrogen-coupled peptide transporter (PEPTl) located in the intestinal apical cell membrane. Because there are 20 amino acids, there may be 400... 

Enterocytes of the intestinal membrane do not have transporters to carry polypeptides and proteins across the intestinal membrane, and they certainly cannot permeate through tight junctions because of their size. Also, polypeptides and proteins are substrates for luminal, brush border, and cytolytic enzymes. Therefore, as illustrated in Table 3, peptide/protein drugs are poorly absorbed across the GI tract. 

DHCC acts like a steroidal hormone. It enters the small intestinal muscosal cell and binds to the nuclear membrane, stimulating the formation of a messenger RNA that diffuses back to the cytosol and directs the formation of several peptides. These are then assembled to form a calcium-binding protein that controls calcium absorption and transport by the small intestine (F5, H12). Besides its role in... 

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