title: Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum.
abstract: The adenosine A(2A) receptor (A(2A) R) is a potential drug target for the treatment of Parkinson's disease and other neurological disorders. In rodents, the therapeutic efficacy of A(2A) R modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A(2A) R localization in the primate basal ganglia and to assess the degree of A(2A) R/mGluR5 colocalization in the striatum. A(2A) R immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A(2A) R immunoreactivity. At the electron microscopic level, striatal A(2A) R labeling was most commonly localized in postsynaptic elements (58% ± 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% ± 5%) or glial (27% ± 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A(2A) R immunoreactivity. Striatal A(2A) R/mGluR5 colocalization was commonly found; 60-70% of A(2A) R-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A(2A) R in the primate basal ganglia and demonstrate that A(2A) R and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A(2A) R could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism.
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Bogenpohl
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Ritter
authors.forename: Randy A
authors.initials: RA
authors.lastname: Hall
authors.forename: Yoland
authors.initials: Y
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001479:Basal Ganglia / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D003712:Dendrites / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005917:Globus Pallidus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D057809:HEK293 Cells; D000882:Haplorhini; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D043705:Receptor, Adenosine A2A; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate