Absorptive cell basolateral membrane

As demonstrated above, the uptake of [1-C at the apical membrane of differentiated Caco-2 cells occurs via a saturable, facilitated mechanism and is inhibited by Ezetimibe, a clinically used inhibitor of cholesterol absorption. Carotenoids secreted at the basolateral membrane were associated... 

Polarized tissues directly involved in drug absorption (intestine) or excretion (liver and kidney) and restricted drug disposition (blood-tissue barriers) asymmetrically express a variety of different drug transporters in the apical or basolateral membrane resulting in vectorial dmg transport. This vectorial dmg transport is characterized by two transport processes the uptake into the cell and subsequently the directed elimination out of the cell (Figure 15.3). Because the uptake of substances... 

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.

Compounds can cross biological membranes by two passive processes, transcellu-lar and paracellular mechanisms. For transcellular diffusion two potential mechanisms exist. The compound can distribute into the lipid core of the membrane and diffuse within the membrane to the basolateral side. Alternatively, the solute may diffuse across the apical cell membrane and enter the cytoplasm before exiting across the basolateral membrane. Because both processes involve diffusion through the lipid core of the membrane the physicochemistry of the compound is important. Paracellular absorption involves the passage of the compound through the aqueous-filled pores. Clearly in principle many compounds can be absorbed by this route but the process is invariably slower than the transcellular route (surface area of pores versus surface area of the membrane) and is very dependent on molecular size due to the finite dimensions of the aqueous pores. 

Iron crosses the luminal membrane of the intestinal mucosal cell by two mechanisms active transport of ferrous iron and absorption of iron complexed with heme (Figure 33-1). The divalent metal transporter, DMT1, efficiently transports ferrous iron across the luminal membrane of the intestinal enterocyte. The rate of iron uptake is regulated by mucosal cell iron stores such that more iron is transported when stores are low. Together with iron split from absorbed heme, the newly absorbed iron can be actively transported into the blood across the basolateral membrane by a transporter known... 

Absorption Epithelial cells Blood Everted sac, Ussing-chamber experiments using intestinal epithelium, basolateral membrane vesicles, Caco-2 cells monolayer... 

The small intestine contains a wide variety of transporters (amino acid transporters, oligopeptide transporters, glucose transporters, lactic acid transporters etc.) on the apical membrane of the epithelial cells, which serve as carriers to facilitate nutrient absorption by the intestine. On the basolateral membrane, the presence of amino acid and oligopeptide transporters has been demonstrated. Active transport mechanisms for di- and tri-peptides have also been demonstrated in the nasal and buccal epithelia. 

In the bloodstream, ferric iron binds tightly to circulating plasma transferrin (TF) to form diferric transferrin (FeTF). Absorption of iron into erythrocytes depends on basolateral membrane receptor-mediated endocytosis of FeTF by transferrin receptor 1 (TfR 1). FeTF binds to TfR 1 on the surface of erythroid precursors. These complexes invaginate in pits on the cell surface to form endosomes. Proton pumps within the endosomes lower pH to promote the release of iron into the cytoplasm from transferrin. Once the cycle is completed,TF and TfR 1 are recycled back to the cell surface. TF and TfR 1 play similar roles in iron absorption at the basolateral membrane of crypt enterocytes (Parkilla et al., 2001 Pietrangelo, 2002). 

In addition to factors Influencing luminal uptake of zinc, transfer across the basolateral membrane has been shown to be dependent on the concentration of albumin in the portal circulation (33). These investigations suggest that metabolic factors which affect the albumin concentration in the plasma may also affect the rate of portal zinc transfer. It should be noted that EDTA did not enhance zinc accumulation within the mucosal cells yet it Increased transfer to the vascular perfusate. These results suggest that basolateral membrane transport of zinc is enhanced by EDTA. We have proposed (35), as has Davies (38), that basolateral transport to the circulation is the rate limiting phase of zinc absorption. Since EDTA and zinc might be transported as a complex (42), the latter may transverse this barrier more easily and thus Increase zinc absorption. 

The absorption of thiamin is impaired in alcoholics, leading to thiamin deficiency (Section 6.4.4). In vitro, tissue preparations show normal uptake of the vitamin into the mucosal cells in the presence of ethanol, but impaired transport to the serosal compartment. The sodium-potassium-dependent ATPase of the basolateral membrane responsible for the active efQux of thiamin into the serosal fluid is inhibited by ethanol (Hoyumpa et al., 1977). 

As a class of tissue, epithelia demarcate body entry points, predisposing a general barrier function with respect to solute entry and translocation. The intestine is lined with enterocytes, which are polarized cells with their apical membrane facing the intestinal lumen that is separated by tight junctions from the basolateral membrane that faces the subepithelial tissues. In addition to their barrier function, the epithelia that line the GI tract serve specialized functions that promote efficient nutrient digestion and absorption and support other organs of the body in water, electrolyte, and bile salt homeostasis. The homeostatic demand on GI tissue that results from this dual function may pose special transport consideration compared with solute translocation across biologically inert barriers. 

FIGURE 2.49 An absorptive cell of the viUus. The part of the plasma membrane facing the lumen is the apical membrane, whereas that facing the blood supply is the basal and lateral (basolateral) membrane. The membrane-bound proteins used to mediate the uptake of a variety of nutrients requires the simultaneous co-transport of sodium ions. The diagram reveals that the transport of glucose cind amino acids is dependent on sodium ions. Sodium-independent transport systems also exist for many nutrients. The sodium depicted in the figure is supplied by intestinal secretions and need not be supplied by any particular diet. 

---