[The mechanisms of depression by benzodiazepines, barbiturates and propofol of excitatory synaptic transmissions mediated by adenosine neuromodulation].
Adenosine is known to modulate synaptic functions through adenosine receptors and the related adenosine neuromodulatory system. Benzodiazepines, barbiturates and propofol, the main actins of which are facilitation of GABAA receptor functions, also facilitate accumulation of endogenous adenosine in the extracellular space by inhibiting adenosine uptake via adenosine transporters. The accumulated adenosine depresses excitatory synaptic transmission by decreasing transmitter release, depressing postsynaptic sensitivity and inhibiting neuronal excitability through adenosine A1 receptors and the related adenosine neuromodulatory system. The adenosine-induced depressions of excitatory synaptic transmissions probably contribute to the mechanisms of the anesthetic, sedative, anticonvulsant and neuroprotective effects of these anesthetics and sedatives. An understanding of the synaptic mechanisms of these anesthetics and sedatives through the adenosine neuromodulatory system is needed for rational clinical use of the drugs.
Narimatsu
Eichi
E
Department of Anesthesiology and Traumatology and Critical Care Medicine, Sapporo Medical University School of Medicine.
Niiya
Tomohisa
T
Kawamata
Mikito
M
Namiki
Akiyoshi
A
D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D003864:Depression, Chemical; D006801:Humans; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D001463:Barbiturates; D018377:Neurotransmitter Agents; D018047:Receptors, Purinergic P1; D001569:Benzodiazepines; D000241:Adenosine; D015742:Propofol