Nucleoside transporter protein

Viswanadhan VN, Ghose AK and Weinstein JN. Mapping the binding site of the nucleoside transporter protein a 3D-OSAR study. Biochim Biophys Acta 1990 1039 356-66. 

Yao, S. Y., Ng, A. M., Muzyka, W. R. et al. (1997). Molecular cloning and functional characterization of nitrobenzylthioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENTl and rENT2) from rat tissues. /. Biol. Chem. 272 (45), 28423-30. 

Huang, Q. Q., et al. Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein. J. Biol. Chem. 1994, 269, 17757-17760. 

Adenosine is not a classical neurotransmitter because it is not stored in neuronal synaptic granules or released in quanta. It is generally thought of as a neuromodulator that gains access to the extracellular space in part from the breakdown of extracellular adenine nucleotides and in part by translocation from the cytoplasm of cells by nucleoside transport proteins, particularly in stressed or ischemic tissues (Fig. 17-2C). Extracellular adenosine is rapidly removed in part by reuptake into cells and conversion to AMP by adenosine kinase and in part by degradation to inosine by adenosine deaminases. Adenosine deaminase is mainly cytosolic but it also occurs as a cell surface ectoenzyme. 

Adenosine and inosine can be transported across cell membranes in either direction, facilitated by a membrane-associated nucleoside transport protein. Concentrative transporters have also been identified. Messenger RNA for a pyrimidine-selective Na+-nucleoside cotransporter (rCNTl) and a purine-selective Na+-nucleoside cotransporter (rCNT2) are found throughout the rat brain. Most degradation of adenosine is intracellular, as evidenced by the fact that inhibitors of adenosine transport, such as dipyridamole, increase interstitial levels of adenosine. Dipyridamole is used clinically to elevate adenosine in coronary arteries and produce coronary vasodilation. In high doses, dipyridamole can accentuate adenosine-receptor-mediated actions in the CNS, resulting in sedation and sleep, anticonvulsant effects, decreased locomotor activity and decreased neuronal activity. 

Jennings LL, Hao C, Cabrita MA, Vickers ME, Baldwin SA, et al. 2001. Distinct regional distribution of human equili-brative nucleoside transporter proteins 1 and 2 (hENTl and hENT2) in the central nervous system. Neuropharmacology 40 722-731. 

An increase of intracellular adenosine levels can also be achieved by inhibition of nucleoside transport proteins. Mammalian nucleoside transport processes can be classified into two types on the basis of their thermodynamic properties. These classes are the concentrative, Na+-dependent transport processes and the equilibrative, Na+-independent processes. The corresponding transporters are called CNTs (concentrative nucleoside transporters) and ENTs (equilibrative nucleoside transporters) (Pastor-Anglada and Baldwin, 2001). 

Molina-Areas M, Trigueros-Motos L, Casado FJ, Pastor-Anglada M (2008) Physiological and pharmacological roles of nucleoside transporter proteins. Nucleosides Nucleotids Nucleic Acids 27(6) 769-778... 

Figure 2.4 Structures of selected nucleoside-derived anticancer and antiviral drugs and their corresponding nucleoside transporter proteins. When it is known, apparent value is given.

Other important renal transport systems include the peptide transporters, which are involved in the uptake of peptide-like drugs including /3 -lactam antibiotics and angiotensin-converting enzyme inhibitors, and nucleoside transporter proteins, which are involved in uptake of nucleosides and nucleoside analogs (e.g., zidovudine and dideoxyinosine). ... 

Nucleosides and nucleoside analogs are used in antiviral and anticancer drug therapy. These drugs generally are hydrophilic in nature and require specialized transport proteins to facilitate their uptake and/or release from the cell. Nucleoside transporters are thought to play a key role in the disposition and nucleosides and nucleoside analogs. There are two families of nucleoside transport proteins, concentrative nucleoside transporters (GNT) and equilihrative nucleoside transporters (ENT). 

Patching SG, Baldwin SA, Baldwin AD, Young JD, Gallagher MP, Henderson PJ, Herbert RB. The nucleoside transport proteins, NupC and NupG, from Escherichia coli specific structural motifs necessary for the binding of ligands. Org. Biomol Chem. 2005 3 462 70. 

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