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

lower levels in other brain regions. A2B possess low levels of expression
in the brain. A3 has apparently intermediate levels of expression in
the human cerebellum and hippocampus and low levels in most of

the brain (31). The well known striatal A2A/D2 receptor interactions
may offer new therapeutic leads for basal ganglia disorders, such

as Parkinson’s disease and Huntington’s chorea, as well as for

schizophrenia (31). Inhibition of D2 receptors in the ventral striatum
seems to be associated with the antipsychotic effect of neuroleptics,

while inhibition of dopamine D2 receptors in the dorsal striatum
is related to their extrapyramidal side effects. In the periphery,

the interaction of A2A receptors with other receptors that regulate
acetylcholine release from motor nerve terminals could reveal the

importance of A2A receptors when deficits in acetylcholine release
occur (e.g. myasthenic syndromes). The excitatory effects of A2A
receptors on acetylcholine release might prove useful when developing

cognitive enhancers that by increasing acetylcholine release could be

of therapeutic interest in dementia (e.g. Alzheimer’s disease). Since

the adenosine A1 receptors inhibit neurotransmitter release, and
inhibit A2A receptor functioning, one can also predict that adenosine-
related medicines that combine adenosine A1 receptor blockade with
A2A receptor activation will be useful in situations where an increase
in neurotransmitter release is needed. There are also situations where

A2A receptor activation might prove to be excitotoxic (e.g. increase in
glutamate release) and, therefore, A2A antagonism will be needed (31).

It is worth noting that after several years of concentrating most

of the adenosine research efforts on adenosine A1 receptors, the
adenosine A2A prove to be a very promising receptor in terms of
understanding the subtle ways used by this nucleoside to implement

a harmonic and fine control of synaptic activity.

Although adenosine is not a neurotransmitter on its own, it shares

via A1 activation many properties attributed to the major inhibitory
neurotransmitter —GABA, i.e. decreases excitability mediated

by glutamate—. So GABA and adenosine constitute key molecules

in the control of glutamatergic synaptic transmission in the central

nervous system (see above). Adenosine is able to functionally

disconnect GABAergic interneurones by inhibiting their glutamatergic

input, a process that might be particularly relevant under conditions

of intense adenosine release, such as it happens during hypoxia. Thus,

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