title: Are A3 adenosine receptors expressed in the brain?
abstract: An increasing number of reports suggest a role for A3 adenosine receptors (A3ARs) in mediating adenosine action in the central nervous system. However, studies of A3AR localization in the brain have yet to be performed. To provide insights into the central sites of A3AR action, we compared patterns of A1 and A3AR mRNA and binding site expression in the brains of rats, mice and humans. We also assessed whether A3 agonists are selective for A3ARs. Whereas it was possible to detect high-level A1AR expression in many brain regions, it was not possible to detect either A3AR gene or binding site expression in the central nervous system. When we examined the affinities of the A3AR agonists CI-IAB-MECA and IAB-MECA for A1ARs, we found that these compounds bound to A1ARs with high affinity. These observations suggest that studies using A3-agonists need to consider potential effects of A1ARs activation, as A1ARs are abundantly expressed in the nervous system whereas A3AR expression in the brain cannot be directly demonstrated.
authors.affiliation: Department of Pediatrics, Yale University Medical School, New Haven, CT 06520, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Rivkees
authors.forename: S
authors.initials: S
authors.lastname: Thevananther
authors.forename: H
authors.initials: H
authors.lastname: Hao
mesh_terms: D000368:Aged; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1