Distribution of CNT2 and ENT1 transcripts in rat brain: selective decrease of CNT2 mRNA in the cerebral cortex of sleep‐deprived rats

Abstract

Nucleoside transport processes regulate the levels of adenosine available to modulate neurotransmission, vascular tone and other physiological events. However, although equilibrative transporter transcripts or proteins have been mapped in the central nervous system of rats and humans, little is known about the presence and distribution of the complete family of nucleoside transporters in brain. In this study, we analysed the distribution of the transcript encoding the high affinity adenosine-preferring concentrative transporter CNT2 in the rat central nervous system and compared it with that of the equilibrative transporter ENT1. Furthermore, we evaluated the changes in expression of these two transporters in a situation of increased extracellular levels of adenosine, such as sleep deprivation. CNT2 mRNA was widespread in rat brain, although most prevalent in the amygdala, the hippocampus, specific neocortical regions and the cerebellum. The distribution of CNT2 mRNA only partially overlapped that of ENT1. Most of the cells labelled were neurones. Total sleep deprivation dramatically diminished the amounts of CNT2 mRNA, whereas ENT1 mRNA remained unchanged. This specific decrease in CNT2 transcript suggests a new physiological role for the transporter in the modulation of extracellular adenosine levels and the sleep/ wakefulness cycle.

Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light

“…ENT1 expression is very low in the hypothalamus (Guillen-Gomez et al, 2004), and therefore may not be a significant source of extracellular adenosine in the SCN. Thus, ENT1 deletion would not be expected to greatly alter SCN adenosine tonus.…”

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

“…Indeed, prolonged wakefulness is known to increase Ado levels in the basal forebrain that, in turn, may decrease the activity of cholinergic cells to promote sleep (Porkka-Heiskanen and Kalinchuk 2011 ) . A selective decrease in CNT2 mRNA levels was demonstrated in the cerebral cortex of sleep-deprived rats (Guillén-Gómez et al 2004 ) . These data suggest that adenosine receptor agonists and nucleoside transport inhibitors might be effective in the treatment of sleep disorders (Table 29.2 ).…”

Transport Mechanisms of Nucleosides and Nucleoside Analogues ReverseTranscriptase Inhibitors in the Brain

“…In situ hybridization revealed that neurons in the hippocampus, basal ganglia, cerebral cortex, hypothalamus and cerebellum had intense signal (GuillenGomez et al, 2004). Interestingly, in situ studies showed that CNT2 mRNA was not present in astrocytes (Guillen-Gomez et al, 2004), but it was present in primary cultures of mouse and rat astrocytes and functional activity of this transporter in those cells was revealed (Nagai et al, 2005, Peng et al, 2005, Redzic et al, 2010b. However, rCNT2 protein was absent from rat astrocytes in primary culture (Redzic et al, 2010b).…”