Striatal Restricted Adenosine A₂ Receptor (RDC8) Is Expressed by Enkephalin but Not by Substance P Neurons: An In Situ Hybridization Histochemistry Study

Abstract

RDC8 has been recently cloned and characterized as an adenosine A2 receptor. This receptor is expressed exclusively by medium-sized neurons of the striatum as demonstrated by in situ hybridization. We have now studied the relationship of this receptor with three major components of the rat caudate-putamen: enkephalin, substance P, and choline acetyltransferase. Our results demonstrate that the adenosine A2 receptor is expressed exclusively by the enkephalinergic striatal subpopulation but not by the substance P-containing or cholinergic neurons.

Stimulation of Adenosine Receptors Selectively Activates Gene Expression in Striatal Enkephalinergic Neurons

“…Furthermore, A 1 -A 2A receptor co-stimulation induced an increase in the expression of the neuropeptide gene preproenkephalin, but not preprodynorphin. These were expected findings given the fact that GABAergic enkephalinergic neurons show the highest expression of A 2A receptors in the brain (Schiffmann et al, 1991;Hettinger et al, 2001). Adenosine A 2A receptors are Gs-olf protein-coupled receptors whose main signaling pathway is adenylyl-cyclase activation, the cAMP-PKA cascade (Kull et al, 1999(Kull et al, , 2000.…”

Simultaneous Blockade of Adenosine A2A and Metabotropic Glutamate mGlu5 Receptors Increase their Efficacy in Reversing Parkinsonian Deficits in Rats

“…In contrast to the widespread distribution of other adenosine receptor subtypes (A 1 , A 2B , and A 3 ), the A 2A receptor subtypes shows a quite specific localization in the basal ganglia largely restricted to the striatum (Svenningsson et al, 1999;Fredholm et al, 2001). As shown by in situ hybridization and binding studies (Martinez-Mir et al, 1991;Schiffmann et al, 1991;Svenningsson et al, 1998), the A 2A receptor is coexpressed with DA D 2 receptors in the striatopallidal GABAergic neurons, which contain enkephalin and originate in the so-called striatal efferent indirect pathway (Fink et al, 1992). Behavioral data support the strong A 2A -D 2 receptor interactions to explain the enhancement of the antiParkinsonian effects of DA agonists in rodent models of PD (Pinna et al, 1996;Fenu et al, 1997;Koga et al, 2000;Hauber et al, 2001).…”

“…In addition, group I mGlu receptors are present in the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) (Tallaksen-Greene et al, 1998;Testa et al, 1994). In the striatum, adenosine A 2A receptors are predominantly expressed by g-amino butyric acid (GABA)-enkephalin striatopallidal neurons, where they colocalize with DA D 2 receptors (Fink et al, 1992;MartinezMir et al, 1991) and are also present in 25% of cholinergic interneurons (Schiffmann et al, 1991;Fredholm et al, 2001). Interestingly, mGlu 5 receptors show a striking similar localization in the striatopallidal GABAergic projection neurons and interneurons in primates , so providing a morphological basis for the possible existence of functional interactions between striatal A 2A and mGlu 5 receptors.…”

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

“…Recent studies also have highlighted the involvement of the purine nucleoside adenosine in this type of function . Although there are at least four types of adenosine receptors, adenosine A 2A receptors are primarily localized in striatal areas, including both neostriatum and nucleus accumbens (Jarvis and Williams 1989;Schiffmann et al 1991;DeMet and Chicz-DeMet 2002;Ferré et al 2004). In these striatal areas, there is considerable evidence of a functional interaction between dopamine D 2 and adenosine A 2A receptors (Fink et al 1992;Ferré 1997;Hillion et al 2002;Fuxe et al 2003).…”