title: The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors.
abstract: We have determined the binding affinities of the novel alpha-2 adrenoceptor antagonist radioligand [3H]-MK912 for the cloned human alpha-2A, alpha-2B and alpha-2C adrenoceptors. The KD-values were 1.25 nM, 1.36 nM and 0.086 nM for the alpha-2A, alpha-2B and alpha-2C subtypes, respectively. Thus, the selectivity of [3H]-MK912 for the human alpha-2C adrenoceptor vs. the human alpha-2A and alpha-2B adrenoceptors is 14-fold and 16-fold, respectively. The alpha-2C selectivity, and the very high affinity of [3H]-MK912 for the alpha-2C adrenoceptor subtype (KD = 86 pM) makes this radioligand a promising tool for studying the role of alpha-2C adrenoceptors in the human. A selection of antagonists useful for differentiating between the human alpha-2A, alpha-2B and alpha-2C adrenoceptor subtypes is discussed.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor.
authors.forename: S
authors.initials: S
authors.lastname: Uhlén
authors.forename: A C
authors.initials: AC
authors.lastname: Porter
authors.forename: R R
authors.initials: RR
authors.lastname: Neubig
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003984:Dibenzazepines / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D054833:Isoindoles; D011807:Quinolizines / Q000378:metabolism*; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D003984:Dibenzazepines; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D011807:Quinolizines; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; C072126:BRL 41992; C072125:BRL 44408