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J. A. RIBEIRO AN. R. ACAD. NAC. FARM.

first to describe that adenosine inhibits neurotransmitter release and
this was done using as a synapse the Rat Neuromuscular Junction
(12, 13). When I arrived in Edinburgh, Bernard Ginsborg asked me
to continue this work in another model —the Frog Neuromuscular
Junction— (32, 33), since in this model there is no margin of safety,
making this nicotinic cholinergic synapse more similar to the central
excitatory synapses, now known to be the glutamatergic synapses.

ADENOSINE AND THE CENTRAL NERVOUS
SYSTEM SYNAPSES

As described for its action on endplate potentials (EPPs),
adenosine at the frog neuromuscular junction, inhibited the
amplitude of the excitatory post-synaptic potentials (EPSPs) recorded
from the Guinea pig Olfactory cortex slices, as first described by
Okada & Kuroda (22). This work has been followed by the work of
Dunwiddie’s group, Stone’s group using rat hippocampal slices, as
well as by my group, in several publications since 1985 (see list in
PubMed), where it was described that the A1-receptor inhibitory
effects of adenosine and adenosine analogues on glutamatergic
transmission, possess almost all characteristics of those previously
observed using the frog neuromuscular junction as a model of
synaptic transmission.

Endogenous Adenosine

Adenosine antagonism, adenosine uptake inhibition, adenosine
deaminase, 5’-ecto-nucleotidase inhibition were used to manipulate
and to recognize the role of endogenous adenosine (29). In parallel
we came across with the existence of A2A excitatory effects at the
neuromuscular junction (29) and in the hippocampus, the first
description was the effect of an A2A agonist (CGS21680) on rat
hippocampal glutamatergic synaptic transmission (35). This was
further supported by in situ hybridization autoradiograms, which
confirmed the co-expression of A1 and A2A in hippocampal brain
slices. The relative importance of A2A receptors vis à vis A1 receptors
in the hippocampus was shown in 1996 when A2A receptors prove to

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