Abstract
Indirect experimental evidence suggests that drugs acting on the alpha(2C)-adrenoceptor could be useful in the treatment of neuropsychiatric disorders such as depression and schizophrenia. In rodent brain, the highest levels of alpha(2C)-adrenoceptors are found in the striatum, with lower levels in cerebral cortex and hippocampus. In human brain, because of the poor subtype-selectivity of the available alpha(2)-adrenoceptor ligands, the localization of alpha(2C)-adrenoceptors has remained unknown. Recently, a selective alpha(2C)-adrenoceptor antagonist, JP-1302, was characterized, and to assess the presence of alpha(2C)-adrenoceptors in human brain, we performed competition binding in vitro receptor autoradiography with JP-1302 and the alpha(2)-adrenoceptor subtype nonselective antagonist [ethyl-(3)H]RS79948-197 on rat and human postmortem brain sections. In striatum of both species, JP-1302 vs. [ethyl-(3)H]RS79948-197 competition binding was biphasic, identifying high- and low-affinity binding sites, whereas in cortex and cerebellum, only low-affinity binding sites were detected. The results indicate that a significant portion of the alpha(2)-adrenoceptors in striatum is of the alpha(2C) subtype, whereas non-alpha(2C)-adreocneptors predominate in cortex and cerebellum. Because the alpha(2C)-adrenoceptor subtype distribution pattern appears to be conserved between rodents and humans, results obtained from studies on the role of the alpha(2C)-adrenoceptor in rodent models of neuropsychiatric disorders may be relevant also for human diseases.
Original language | English |
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Pages (from-to) | 508-15 |
Number of pages | 8 |
Journal | Synapse |
Volume | 62 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jul 2008 |
MoE publication type | A1 Journal article-refereed |
Keywords
- Acridines/metabolism
- Adrenergic alpha-Antagonists/metabolism
- Animals
- Autoradiography/methods
- Binding Sites/physiology
- Binding, Competitive/physiology
- Catecholamines/metabolism
- Cerebellum/drug effects
- Cerebral Cortex/drug effects
- Corpus Striatum/metabolism
- Evolution, Molecular
- Humans
- Isoquinolines/metabolism
- Ligands
- Male
- Middle Aged
- Naphthyridines/metabolism
- Phylogeny
- Piperazines/metabolism
- Rats
- Receptors, Adrenergic, alpha-2/analysis
- Species Specificity
- Tritium