title: Alpha 2-adrenoceptor subtypes identified by [3H]RX821002 binding in the human brain: the agonist guanoxabenz does not discriminate different forms of the predominant alpha 2A subtype.
abstract: Competition [3H]RX821002 ([3H]2-methoxyidazoxan) binding experiments with alpha 2-adrenoceptor subtype-specific antagonists--BRL 44408 (alpha 2A selectively), ARC 239 (alpha 2B selective), and others--were performed to delineate through rigorous computer modeling receptor subtypes in the postmortem human brain. In the hippocampus, hypothalamus, cerebellum, and brainstem the whole population of alpha 2-adrenoceptors appears to belong to the alpha 2A subtype (100%; Bmax = 34-90 fmol/mg of protein). In the frontal cortex, the predominant receptor was the alpha 2A subtype (87%; Bmax = 53 fmol/mg of protein), although a small population of the alpha 2B/C subtype (13%; Bmax = 8 fmol/mg of protein) was also detected. In the caudate nucleus, a mixed population of alpha 2A (64%; Bmax = 9 fmol/mg of protein) and alpha 2B/C (36%; Bmax = 5 fmol/mg of protein) subtypes was detected. In the cortex and caudate and in the presence of ARC 239 (to mask the alpha 2B/C-adrenoceptors), competition experiments with the agonist guanoxabenz clearly modeled the high- and low-affinity states of the alpha 2A subtype. In the presence of ARC 239 and the GTP analogue guanylyl-5'-imidodiphosphate together with NaCl and EDTA (to eliminate the high-affinity alpha 2A-adrenoceptor) guanoxabenz only recognized the low-affinity alpha 2A-adrenoceptor. The results indicate that in the human brain the predominant alpha 2-adrenoceptor is of the alpha 2A subtype and that this functionally relevant receptor subtypes is not heterogeneous in nature.
authors.affiliation: Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sastre
authors.forename: J A
authors.initials: JA
authors.lastname: García-Sevilla
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000328:Adult; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004146:Dioxanes / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006143:Guanabenz / Q000031:analogs & derivatives* / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D054833:Isoindoles; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D014316:Tritium
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D007546:Isoquinolines; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D006165:Guanylyl Imidodiphosphate; D012965:Sodium Chloride; D004492:Edetic Acid; C058525:2-methoxyidazoxan; D006143:Guanabenz; C032994:AR-C239; C028782:guanoxabenz; D019329:Idazoxan; C072125:BRL 44408