Genetic interdependence of adenosine and dopamine receptors: evidence from receptor knockout mice.
Dopamine and adenosine receptors are known to share a considerable overlap in their regional distribution, being especially rich in the basal ganglia. Dopamine and adenosine receptors have been demonstrated to exhibit a parallel distribution on certain neuronal populations, and even when not directly co-localized, relationships (both antagonistic and synergistic) have been described. This study was designed to investigate dopaminergic and purinergic systems in mice with ablations of individual dopamine or adenosine receptors. In situ hybridization histochemistry and autoradiography was used to examine the level of mRNA and protein expression of specific receptors and transporters in dopaminergic pathways. Expression of the mRNA encoding the dopamine D2 receptor was elevated in the caudate putamen of D1, D3 and A2A receptor knockout mice; this was mirrored by an increase in D2 receptor protein in D1 and D3 receptor knockout mice, but not in A2A knockout mice. Dopamine D1 receptor binding was decreased in the caudate putamen, nucleus accumbens, olfactory tubercle and ventral pallidum of D2 receptor knockout mice. In substantia nigra pars compacta, dopamine transporter mRNA expression was dramatically decreased in D3 receptor knockout mice, but elevated in A2A receptor knockout mice. All dopamine receptor knockout mice examined exhibited increased A2A receptor binding in the caudate putamen, nucleus accumbens and olfactory tubercle. These data are consistent with the existence of functional interactions between dopaminergic and purinergic systems in these reward and motor-related brain regions.
Department of Pharmacology, Faculty of Medicine, Monash University, Clayton, Victoria 3800, Australia.
J L
JL
Short
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Ledent
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Borrelli
J
J
Drago
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AJ
Lawrence
D000345:Affinity Labels / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics; D017403:In Situ Hybridization / Q000379:methods; D008454:Mazindol / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology; D033703:Nucleoside Transport Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics
D000345:Affinity Labels; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D033703:Nucleoside Transport Proteins; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D014316:Tritium; D013868:Thioinosine; D008454:Mazindol; C001789:4-nitrobenzylthioinosine