Nucleoside transporters: from scavengers to novel therapeutic targets.
Hydrophilic purine and pyrimidine nucleosides rely on specialized carrier proteins for their membrane translocation. The recent identification of two gene families encoding equilibrative and concentrative nucleoside transporters in mammals and other organisms has provided the essential breakthrough to a more complete understanding of the biological significance of nucleoside transport. Although nucleoside salvage is a primary function of these proteins, recent data indicate functions beyond metabolic recycling. In brain and spinal cord, for example, nucleoside transporters have the potential to regulate synaptic levels of neuroactive purines such as adenosine and, thereby, indirectly modulate physiological processes through G-protein-coupled purine P1 receptors. As described in this review, recent research indicates novel putative functions for CNS nucleoside transporters in sleep, arousal, drug and alcohol addiction, nociception and analgesia. The therapeutic use of nucleoside analogue drugs and nucleoside transporter inhibitors in viral, neoplastic, cardiovascular and infectious disease is also described.
King
Anne E
AE
Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. a.e.king@leeds.ac.uk
Ackley
Michael A
MA
Cass
Carol E
CE
Young
James D
JD
Baldwin
Stephen A
SA
D000818:Animals; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D033703:Nucleoside Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry
D033703:Nucleoside Transport Proteins; D004364:Pharmaceutical Preparations