Transporter expression

ABC Transporters. Figure 2 ABC-transporter expression in hepatocytes and enterocytes (modified according to www.iwaki-kk.co.jp/bio/specialedition/se02.htm). 

Mayfield, R.D., Maiya, R., Keller, D., and Zahniser, N.R., Ethanol potentiates the function of the human dopamine transporter expressed in Xenopus oocytes, J. Neurochem., 79, 1070, 2001. 

In this section, we focus on the amino acid transporters expressed in the GI tract. The cationic amino acid transporter CAT family, CAT-1 and LAT-1, are abun-... 

Ihara, T., et al. Regulation of PepTl peptide transporter expression in the rat small intestine under malnour-... 

Pastor-Anglada, M., et al. Complex regulation of nucleoside transporter expression in epithelial and immune system cells. Mol. Membr. Biol. 2001, 18, 81-85. 

Fukumoto, H., et al. Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J. Biol. Chem. 1989, 264, 7776-7779. 

Ibberson, M., M. Uldry, and B. Thorens. GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues. J. Biol. Chem. 2000, 275, 4607-4612. 

Davidson, N. O., et al. Human intestinal glucose transporter expression and localization of GLUT5. Am. J. Physiol. 1992, 262, C795-C800. 

Feild, J. A., et al. Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine. Biochem. Biophys. Res. Commun. 1999, 258, 578-582. 

From the above, it is clear that the gut wall represents more than just a physical barrier to oral drug absorption. In addition to the requirement to permeate the membrane of the enterocyte, the drug must avoid metabolism by the enzymes present in the gut wall cell as well as counter-absorptive efflux by transport proteins in the gut wall cell membrane. Metabolic enzymes expressed by the enterocyte include the cytochrome P450, glucuronyltransferases, sulfotransferases and esterases. The levels of expression of these enzymes in the small intestine can approach that of the liver. The most well-studied efflux transporter expressed by the enterocyte is P-gp. 

This chapter describes some of the modified mammalian cell-based systems that have been developed to express intestinal cytochrome P450 enzymes and intestinal transporters. The reader should be aware that other experimental systems, such as transporter expression and drug uptake studies in Xenopus laevis oocytes, have also shown considerable promise [1],... 

Within the OAT family, OAT4 is the only transporter expressed at appreciable levels in both the placenta and in the kidney [54]. The membrane localization of OAT4 within these tissues has not been examined. Steroid sulfates, and ochratoxinA are efficient transport substrates of OAT4, whereas PAH is weakly transported [54]. The functional importance of OAT4 in regulating placental permeability and renal drug elimination is currently unknown. 

Belinsky MG, Kruh GD. MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter expressed in kidney and liver. Br J Cancer 1999 80(9) 1342-1349. 

P-type copper transporters are important for neural function. Wilson s and Menke s diseases have major neurological components (Ch. 45). The Wilson s disease gene codes for a transporter, expressed chiefly in liver, that probably functions in Cu2+ excretion. The Menke s disease gene codes for a closely related transporter that regulates intestinal Cu2+ absorption [32],... 

Vannucci, S. J., Clark, R. R., Koehler-Stec, E. etal. Glucose transporter expression in brain relationship to cerebral glucose utilization. Dev. Neurosci. 20 369-379,1998. 

Rothstein, J. D., Patel, S., Regan, M. R. etal. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433 73-77,2005. 

Mager, S Naeve, J., Quick, M., Labarca, C., Davidson, N., and Lester, H. A. (1993) Steady states, charge movements, and rates for a cloned GABA transporter expressed in Xenopus oocytes. Neuron 10,177-188. 

Wang, J. B., Moriwaki, A., and Uhl, G. R. (1995) Dopamine transporter cysteine mutants second extracellular loop cysteines are required for transporter expression. J. Neurochem. 64,1416-1419. 

Figure 2.12 Correlation plots of (A) transporter expression and (B) metabolic enzyme expression in duodenum between rat and human. The expression levels of transporters and metabolic enzymes are normalised by GADPH expression, transformed by natural logarithm and absolute values were used in the correlation analysis [121].

Organotypic corneal constructs do resemble the in vivo cornea in many aspects, but they have the drawback of a complex isolation/setup procedure and longer cultivation periods. Additionally, in contrast to the well-established corneal cell lines that have been used for several years, these constmcts are relatively new and further validation of the barrier characteristics and transporter expression/function are needed. Nonetheless, we surmise that both in vitro models are promising tools for evaluating transcorneal drug delivery. 

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