Equilibrative drug transport

In this case, the sequence suggests a 14-TM-helix protein with multiple glycosylation and phosphorylation sites. Although differing in molecular detail, it is likely that all members of the equilibrative and Na -linked families will be similar in overall three-dimensional structure and transport mechanism. However, there is a wealth of detailed variation upon which selectivity in drug transport or transporter inhibition may eventually be based. 

Owen, R.P., Lagpacan, L.L., Taylor, T.R., De LaCruz, M., Huang, C.C., Kawamoto, M., Johns, S.J., Stryke, D., Ferrin, T.E. and Giacomini, KM. (2006) Functional characterization and haplotype analysis of polymorphisms in the human equilibrative nucleoside transporter, ENT2. Drug Metabolism and Disposition The Biological Fate of Chemicals, 34 (1), 12-15. 

Lu, H., Chen, C., and Klaassen, C. (2004) Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice. Drug Metabolism and Disposition, 32 (12), 1455-1461. 

Molina-Arcas, M., Moreno-Bueno, G., Cano-Soldado, P., Hemandez-Vargas, H., Casado, F.J., Palacios, and Pastor-Anglada, M. (2006) Human equilibrative nucleoside transporter-1 (hENTl) is required for the transcriptomic response of the nudeoside-derived drug 5 -DFUR... 

Lai, Y, Tse, C. M., Unadkat, J. D. (2004). Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENTl) results in enhanced mitochondrial toxicity of antiviral drugs. The Journal of Biological Chemistry, 279(6), 4490 497. 

Sundaram M, Yao SY, Ng AM et al. Chimeric constructs between human and rat equilibrative nucleoside transporters (hENTl and rENTl) reveal hENTl structural domains interacting with coronary vasoactive drugs. J Biol Chem 1998 273(34) 21519-21525. 

The neuronal transport system is the most important mechanism for removing norepinephrine. Any norepinephrine or epinephrine in the circulation will equilibrate with the junctional extracellular fluid and thus become accessible both to the receptors and to neuronal transport. Thus, neuronal transport is also an important mechanism for limiting the effect and duration of action of norepinephrine or epinephrine, whether these are released from the adrenal medulla or are administered as drugs. Neuronal uptake is primarily a mechanism for removing norepinephrine rather than conserving it. Under most circumstances, synthesis of new norepinephrine is quite capable of keeping up with the needs of transmission, even in the complete absence of neuronal reuptake. 

Quite apart from the so-called blood-brain barrier (and where it is lacking, e.g. some parts of the pituitary, hypothalamus and brain stem, i.e. the chemoreceptor trigger zone), there are many other factors which govern equilibration of drug concentration between CSF and the parenchyma of the brain itself. The differential effects of P-glyco-protein saturable active transport can govern the CNS sequestration in a manner that is completely unrelated to relative lipophilicity or ambient drug concentration. 

If the outside drug concentration is maintained (Figure 7.5A) internal drug concentration accumulation driven by an active transport process into the cell will eventually equilibrate at concentrations greater than the external concentration. Like facilitated diffusion, active transport mediated flux rate can be saturated at higher drug concentrations (Figure 7.5B). 

Sundaram M, Yao SYM, Ingram JC et al. Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter (hENTl) implicated in the cellular uptake of adenosine and anti-cancer drugs. J Biol Chem 2001 276 45270-45275. 

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