title: Role of adenosine A1 receptors in the modulation of dopamine D1 and adenosine A2A receptor signaling in the neostriatum.
abstract: Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A(2A) receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) at Thr34 (the cAMP-dependent protein kinase [PKA] site) in striatopallidal neurons, and opposes dopamine D2 receptor signaling. In contrast, the role of adenosine A(1) receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A(1) receptors on D(1), D(2) and A(2A) receptor signaling using mouse neostriatal slices. An A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (100 nM), caused a transient increase, followed by a transient decrease, in DARPP-32 Thr34 phosphorylation. Our data support the following model for the actions of the A(1) receptor agonist. The A(1) receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D(2) receptors of A(2A) receptor/G(olf)/cAMP/PKA signaling. The A(1) receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic G(i) mechanism, resulting in inhibition of D(1) and A(2A) receptor-coupled G(olf)/cAMP/PKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A(1) receptors play a major modulatory role in dopamine and adenosine receptor signaling.
authors.affiliation: Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yabuuchi
authors.forename: M
authors.initials: M
authors.lastname: Kuroiwa
authors.forename: T
authors.initials: T
authors.lastname: Shuto
authors.forename: N
authors.initials: N
authors.lastname: Sotogaku
authors.forename: G L
authors.initials: GL
authors.lastname: Snyder
authors.forename: H
authors.initials: H
authors.lastname: Higashi
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: A
authors.initials: A
authors.lastname: Nishi
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013912:Threonine / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D001552:Benzazepines; D018492:Dopamine Antagonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D013912:Threonine; C058394:2-chloro-N(6)cyclopentyladenosine; D020891:Raclopride; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine