Regulation of adenosine levels during cerebral ischemia.
Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events, and attenuates the excitotoxic neuronal injury. Adenosine is produced both intracellularly and extracellularly, and nucleoside transport proteins transfer adenosine across plasma membranes. Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption, cellular release of ATP, metabolism of extracellular ATP (and other adenine nucleotides), adenosine influx, adenosine efflux and adenosine metabolism. Recent studies have used genetically modified mice to investigate the relative contributions of intra- and extracellular pathways for adenosine formation. The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase. From these studies, we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures, but not in hippocampal slices or in vivo mice exposed to ischemic conditions.
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada.
Stephanie
S
Chu
Wei
W
Xiong
Dali
D
Zhang
Hanifi
H
Soylu
Chao
C
Sun
Benedict C
BC
Albensi
Fiona E
FE
Parkinson
D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D033703:Nucleoside Transport Proteins / Q000378:metabolism
D033703:Nucleoside Transport Proteins; D000255:Adenosine Triphosphate; D000241:Adenosine