Page 138 - 69_04

B. B. FREDHOLM ANAL. REAL ACAD. NAL. FARM.

FIGURE 2. Schematic illustration of the interactions between adenosine and dopamine

The next major conceptual advance was the cloning of several
adenosine receptors, as described above. These findings not only
conclusively proved that there are two distinct adenosine A2 receptors, but
also provided a set of novel tools that proved very useful. In situ
hybridisation was used to pinpoint the cells that express A2A receptors in
the brain. Using increasingly sophisticated methods it was proven that the
bulk of A2A expression is confined to one set of neurones in the striatum,
namely those GABAergic output neurons that constitute the so-called
indirect pathway (Schiffmann, Jacobs and Vanderhaeghen; 1991,
Schiffmann, Libert, Vassart and Vanderhaeghen; 1991, Fink et al.; 1992,
Johansson, Ahlberg, van der Ploeg, Brené, Lindefors, Persson and
Fredholm; 1993, Pollack, Harrison, Wooten and Fink; 1993, Johansson,
Georgiev and Fredholm; 1997, Svenningsson, Le Moine, Kull, Sunahara,
Bloch and Fredholm; 1997). These cells also express the bulk of the
dopamine D2 receptors. Hence the link between A2A and dopamine D2
receptors was further strengthened.

Techniques with a cellular resolution were also used to try to determine
the roles of adenosine A2A receptors in the intact striatum. This was based

150