Alpha 2-adrenoceptor subtypes in the human brain: a pharmacological delineation of [3H]RX-821002 binding to membranes and tissue sections.
In order to study the characterization and localization of [3H]RX-821002 (2-methoxy-idazoxan) binding to alpha 2-adrenoceptor subtypes in several regions of the human brain, we have carried out competition studies using both autoradiography and membrane binding assays. The alpha 2A-adrenoceptor subtype was found to be predominant in the different layers of the frontal cortex, cerebellum and hippocampal formation, while in the neostriatum it was the non-alpha 2A- (alpha 2B- and alpha 2C-) adrenoceptor subtype. In the frontal cortex, in addition to binding to the alpha 2A-adrenoceptor subtype, [3H]RX-821002 bound also to a small portion of alpha 2B- and alpha 2C-adrenoceptors in layer III, and to an unidentified binding site in the external layers. In the hippocampus, both alpha 2A- and non-alpha 2A- (alpha 2B- and alpha 2C-) adrenoceptors were labelled in the dentate gyrus and the CA1 field, together with 5-HT1A receptors. 5-HT1A receptors were labelled predominantly in the stratum pyramidale layer. These results, in addition to delineate the relative presence of alpha 2-adrenoceptor subtypes, indicate that caution is needed when analyzing RX 821002 binding to human brain tissue.
Grijalba
B
B
Department of Physiology and Pharmacology, University of Cantabria, Santander, Spain.
Callado
L F
LF
Javier Meana
J
J
García-Sevilla
J A
JA
Pazos
A
A
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000328:Adult; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D009928:Organ Specificity; D011869:Radioligand Assay
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; C058525:2-methoxyidazoxan; D019329:Idazoxan; C072125:BRL 44408