Adenosine mediation of presynaptic feedback inhibition of glutamate release.
Conditions of increased metabolic demand relative to metabolite availability are associated with increased extracellular adenosine in CNS tissue. Synaptic activation of postsynaptic NMDA receptors on neurons of the cholinergic brainstem arousal center can increase sufficient extracellular adenosine to act on presynaptic A1 adenosine receptors (A1ADRs) of glutamate terminals, reducing release from the readily releasable pool. The time course of the adenosine response to an increase in glutamate release is slow (tau > 10 min), consistent with the role of adenosine as a fatigue factor that inhibits the activity of cholinergic arousal centers to reduce arousal.
Brambilla
Dario
D
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Chapman
David
D
Greene
Robert
R
D000241:Adenosine / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D000241:Adenosine