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Purinoceptors and synaptic plasticity
Author(s) -
Ribeiro J. Alexandre,
de Mendonça Alexandre,
CorreiadeSá Paulo,
Cunha Rodrigo A.,
Sebastião Ana M.
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199611/12)39:3/4<353::aid-ddr16>3.0.co;2-2
Subject(s) - adenosine , neuroscience , inhibitory postsynaptic potential , long term potentiation , excitatory postsynaptic potential , synaptic plasticity , chemistry , neurotransmission , adenosine a2a receptor , long term depression , adenosine receptor , adenosine a1 receptor , nmda receptor , stimulation , biology , receptor , ampa receptor , agonist , biochemistry
Adenosine is considered an important modulator of the nervous system acting at pre‐, post‐, and nonsynaptic levels. In models (e.g. the rat neuromuscular junction) where adenosine has only presynaptic (inhibitory, which are A 1 ‐receptor mediated; and excitatory, which are A 2A ‐receptor mediated) effects, the action of adenosine on transmitter release depends on the intensity of stimulation. It is inhibitory with low frequencies of stimulation and excitatory with high frequencies of stimulation. This finding suggests that the presynaptic adenosine A 1 /A 2A receptor activation balance depends on the pattern of stimulation. At the rat hippocampal slices, endogenous adenosine inhibits the neurophysiological basis of learning and memory: long‐term potentiation (LTP), long‐term depression (LTD), and depotentiation. Adenosine A 2A agonists facilitate LTP. Because the adenosine analogue 2‐chloroadenosine in low concentrations (100 nM) inhibits N‐methyl‐D‐aspartate (NMDA) currents in pyramidal cells, it is likely that the inhibitory effects of adenosine on LTP and LTD/depotentiation are a consequence of its ability to inhibit NMDA currents. The modulatory actions of adenosine on synaptic plasticity support the role of this nucleoside in cognition, and therefore, A 1 antagonists and A 2A agonists could be considered as potential cognitive enhancers. The adaptation of adenosine to activate presynaptic A 1 or A 2A receptors at low or high frequencies of stimulation anticipates the potential interest of A 1 antagonists and A 2A agonists as enhancers of neuromuscular transmission. Drug Dev. Res. 39:353–360, 1996. © 1997 Wiley‐Liss, Inc.