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VOL. 69 (4) ADENOSINE RECEPTORS

The distribution of receptors tells us where agonists and
antagonists given to the intact organism can act. Furthermore, the rather
low levels of endogenous adenosine present under basal physiological
conditions have the potential of activating receptors where they are
abundant, but not where they are sparse (Svenningsson, Nomikos and
Fredholm; 1999).

There is much information on the distribution of the A1 and A2A
receptors from several different species, because good pharmacological
tools including radioligands (see below) are available. There are also
several studies that have used antibodies to localize adenosine A1 and A2A
receptors receptors in brain (Rosin, Robeva, Woodard, Guyenet and
Linden; 1998, Hettinger, Lee, Linden and Rosin; 2001). In the case of the
A2B and A3 receptors the data are less impressive. Here one tends to rely
on data on the expression of the corresponding mRNA. Some of this
information is summarized in Table 1.

Adenosine A1 receptor mRNA is widespread in the brain, with the
highest levels in cell bodies in hippocampus, cerebellum and cerebral
cortex (Mahan et al.; 1991, Reppert, Weaver, Stehle and Rivkees; 1991).
Studies using immunohistochemistry and ligand autoradiography have
shown that adenosine A1 receptor protein and the corresponding mRNA
do not exactly match in several regions of the central nervous system
(Johansson, Ahlberg, van der Ploeg, Brené, Lindefors, Persson and
Fredholm; 1993, Swanson et al.; 1995). Much of the differential
distribution can probably be explained by the fact that a substantial
number of adenosine A1 receptors are present at nerve terminals. For
example, a careful examination of the comparative distribution of
adenosine A1 receptor mRNA and protein in hippocampus showed that
this mRNA is enriched in cell bodies in the granular layer of dentate
gyrus and the pyramidal layers of CA1 and CA3, whereas [3H]DPCPX
binding and A1 receptor immunoreactivity is predominantly found in the
dentate hilus stratum moleculare, stratum lacunosum, stratum radiatum
and stratum oriens (Swanson et al.; 1995). Double immunofluorescence
experiments showed that A1 receptor protein co-localize with SMI-31 that
labels axons, but to a lesser extent with MAP2a, b, which labels cell
bodies and dendrites, or with synaptophysin, which labels synapses.

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