Adenosine transport

Aminoimidazole-4-carboxamide ribonucleoside (also known as AICA riboside or AICAR). An adenosine analogue that is taken up into cells by adenosine transporters and converted by adenosine kinase to the monophosphorylated nucleotide form, ZMP. ZMP is an analogue of AMP that activates the AMP-activated protein kinase (AMPK), for which acadesine or AICAR can be used as a pharmacological activator. 

The first pharmacological agent shown to activate AMPK was 5-aminoimidazole-4-carboxamide (AICA) riboside, also known as acadesine. This adenosine analogue is taken up into cells by adenosine transporters and phosphoiylated by adenosine kinase to the mono-phosphorylated form, AICA ribotide or ZMP. ZMP accumulates inside cells to higher concentrations than the concentration of AICA riboside present in the medium, and it mimics both effects of AMP on AMPK system (allosteric activation and inhibition of... 

Pentamidine is an aromatic diamidine. Pentamidine uptake by the parasite is mediated by several different adenosine transporters. The mode of action is unclear. 

Adenosine has been proposed to induce sleep by inhibiting cholinergic neurons of the BFB and the brainstem. In this respect, adenosine and the adenosine transport inhibitor NBTI decrease the discharge rate of BFB neurons during W, whereas the adenosine Ai receptor antagonist CPDX induces the opposite effects (Alam et al., 1999 Strecker et al., 2000). In addition, perfusion of adenosine into... 

Li, J. Y., R. J. Boado, and W. M. Pardridge. Cloned blood-brain barrier adenosine transporter is identical to the rat concentrative Na+ nucleoside cotransporter CNT2. J. Cereb. Blood Flow Metab. 2001, 21, 929-936. 

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. 

Figure 14.3 Integration plot of the initial uptake of [3H]adenosine by the retina after intravenous administration (A) and retinal uptake index (RUI) of [3H]adenosine and [3H]D-mannitol (B). A [3H]Adenosine (10 //.Ci/head) was injected into the femoral vein. B A test compound, [3H]adenosine or [3H]D-mannitol (10 //Ci/head), and a reference compound, [14C]n-butanol (0.1 //Ci/head), were injected into the common carotid artery in the presence or absence of 2 mM inhibitors. p < 0.05, significantly different from the control. Data from Biochimica et Biophysica Acta, 1758, Nagase et al., Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. 13-19, 2006, with permission from Elsevier.

K. Nagase, M. Tomi, M. Tachikawa, and K. Hosoya. Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. Biochim. Biophys. Acta 1758 13-19 (2006). 

There is evidence that in cerebral ischaemia adenosine may have protective effects, since it inhibits the release of many excitatory neurotransmitters, such as glutamate, and it also stabilises the membrane potential. Unfortunately, adenosine has an extremely short half-life, but recently nucleoside (adenosine) transport inhibitors, e.g. draflazine, have been developed that prevent the endothelial uptake and breakdown of adenosine and prolong its beneficial effects. Nucleoside transport inhibitors also have myocardial protective properties and may have a role in organ preservation prior to transplantation. Adenosine also has an antinociceptive function and various adenosine analogues have antinociceptive activity, which correlates with their affinity for the A1 receptors (Lipkowski and co-workers 1996). 

Carter NS, Fairlamb AH. Arsenical-resistant trypanosomes lack an unusual adenosine transporter. Nature 1993 361 173-176. 

Chaudary N, Naydenova Z, Shuralyova I, Coe IR (2004) The adenosine transporter, mENTl, is a target for adenosine receptor signaling and protein kinase Cepsilon in hypoxic and pharmacological preconditioning in the mouse cardiomyocyte cell line, HL-1. J Pharmacol Exp Ther 310(3) 1190-1198... 

Normal PRP Blood was collected in presence of 2= eoxyoof mydn (adenosine deaminase inhibitor) and dilazep (adenosine transport inhibitor) to maintain steady-state levds of dasma adenosine. 

Aguayo, C., Flores, C., Parodi, J., Rojas, R., Mann, G.E., Pearson, J.D., and Sobrevia, L. (2001) Modulation of adenosine transport by insulin in human umbilical artery smooth muscle ceUs from normal or gestational diabetic pregnancies. The Journal of Physiology, 534 (Pt 1), 243-254. 

L. (2006) Nitric oxide reduces adenosine transporter ENTl gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes. Journal of Cellular Physiology, 208 (2),... 

Aguayo, C., Casado, J., Gonzalez, M., Pearson, J.D., Martin, R.S., Casanello, P., Pastor-Anglada, M., and Sobrevia, L. (2005) Equilibrative nucleoside transporter 2 is expressed in human umbilical vein endothelium, but is not involved in the inhibition of adenosine transport induced by hyperglycaemia. Placenta, 26 (8-9), 641-653. 

Shuralyova, 1., and Coe, I.R. (2004) Hypoxia regulates the adenosine transporter, mENTl, in the murine cardiomyocyte cell line, HL-1. Cardiovascular Research, 61 (4), 780-788. 

Valdes, R., Fernandez-Veledo, S., Aymerich, L, Casado, F.J., and Pastor-Anglada, M. (2006) TGF-beta transcriptionally activates the gene encoding the high-affinity adenosine transporter CNT2 in rat liver parenchymal cells. Cellular and Molecular Life Sciences, 63 (21), 2527-2537. 

Fernandez-Veledo, S., Casado, V., Norman, R.I.. Casado, F.J., lluis, C., Franco, R., and Pastor-Ariglada, M. (2004) ATP-sensitive K channels regulate the concentrative adenosine transporter CNT2 following activation hy A] adenosine receptors. Molecular and Cellular Biology, 24 (7), 2710-2719. 

Sakowicz, M., Szutowicz, A., and Pawelczyk, T. (2004) Insulin and glucose induced changes in expression level of nucleoside transporters and adenosine transport in rat T lymphocytes. Biochemical Pharmacology, 68 (7), 1309-1320. 

Melarsoprol resistance likely involves transport defects. The P2 adenine-adenosine transporter has activity on melarsoprol as well as pentamidine and berenil point mutations in this transporter are found in melarsoprol-resistant isolates. 

Witola W H, et al. (2004). RNA-interference silencing of the adenosine transporter-1 gene in Trypanosoma evansi confers resistance to diminazene aceturate. Exp. Para-sitol. 107(1-2) 47-57. 

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