Colon efflux systems

Other cell lines used in permeability studies include the T84 human colonic adenocarcinoma colonic crypt cell model. This line has a reduced carrier expression, secrets mucus, and has very high resistance [31, 32], The IEC cell line is a rat fetal intestinal epithelium cell with higher permeabilities than Caco-2 cells [33], LLC PKi is a pig kidney epithelial cell line with low expression of efflux systems, but expression systems for transport proteins [32], 2/4/A1 cells are a conditionally immortalized rat fetal intestinal epithelium line with crypt cell-like morphology and temperature-sensitive differentiation [34], They form differentiated monolayers with tight junctions, increased brush border enzymes when grown on extracellular matrices with laminin. Transport of drugs with LP in 2/4/A1 monolayers was comparable to that in the human jejunum and up to 300 times faster than that in Caco-2 monolayers. In contrast, the permeability of HP drugs was comparable in both cell lines [34],... 

In recent years, it has been found that the barrier function of the intestinal epithelium cannot be adequately described by a combination of metabolic and physical barriers alone. Apically polarized efflux systems are known to be present in cancer cells and represent a major barrier to the uptake of a wide variety of chemotherapeutic agents (i.e. in multi-drag resistance). Efflux systems have also now been identified in normal intestinal and colonic cells, and also at other epithelial sites. 

A second member of the ceruloplasmin family multicopper oxidases with six BCB domains was recently identified as the causative agent of sex-linked anemia (sla) in mice (Vulpe et al., 1993). It was named hephaes-tin and shown to be expressed mostly in the small intestine and the colon, where it is presumably involved in gastrointestinal iron uptake. Hephaes-tin displays a high level of sequence identity to ceruloplasmin and differs from it only by an additional C-terminal transmembrane domain, which anchors the protein to the cell membrane. A 582-nucleotide in-frame deletion in the mRNA for hephaestin sla mice has been identified compared to normal animals. The mice with such a mutation are unable to release iron from enterocytes (intestinal epithelial cells) into the circulation, which results in severe anemia. The GPI-anchored form of ceruloplasmin could potentially also mediate similar cellular iron efflux in the central nervous system. There is a transferrin-independent iron uptake system that requires Fe(III) to be reduced to Fe(II) at the cell surface for uptake to occur (DeSilva et al., 1996). Ceruloplasmin would oxidize Fe and prevent its uptake by this mechanism. Briefly, the role of ceruloplasmin is most likely to prevent excessive intracellular iron accumulation by tightly controlling iron efflux and inhibiting its uptake. 

Third, most of the available evidence suggests that, at a given soil P concentration, plants growing at elevated [CO2] are capable of maintaining their tissue phosphorus concentrations. This is in contrast to nitrogen and occurs because of the positive effects of larger root systems on the extent of root mycorrhizal colonization, root organic acid efflux per plant, and root acid phosphatase activity. All three processes play important roles in phosphorus acquisition. 

---