A new neuromodulatory pathway with a glial contribution mediated via A(2a) adenosine receptors.
A low concentration (10 nM) of adenosine potentiated hippocampal neuronal activity via A(2a) adenosine receptors without affecting presynaptic glutamate release or postsynaptic glutamatergic conductance. Adenosine inhibited glutamate uptake through the glial glutamate transporter, GLT-1, via A(2a) adenosine receptors. In addition, adenosine stimulated GLT-1-independent glutamate release from astrocytes, possibly in response to a rise in intracellular Ca(2+), via A(2a) adenosine receptors involving PKA activation. Those adenosine actions could lead to an increase in synaptic glutamate concentrations responsible for the potentiation of hippocampal neuronal activity. The results of the present study thus represent a novel neuromodulatory pathway with a glial contribution, bearing both inhibition of GLT-1 function and stimulation of glial glutamate release, as mediated via A(2a) adenosine receptors.
Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan. tamayuki@hyo-med.ac.jp
T
T
Nishizaki
K
K
Nagai
T
T
Nomura
H
H
Tada
T
T
Kanno
H
H
Tozaki
X X
XX
Li
T
T
Kondoh
N
N
Kodama
E
E
Takahashi
N
N
Sakai
K
K
Tanaka
N
N
Saito
D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000172:deficiency / Q000187:drug effects / Q000235:genetics; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D027342:Excitatory Amino Acid Transporter 2; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine; D002118:Calcium