The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 271; no. 3; pp. 1558 - 1565
• Main Authors: Uhlén, S, Porter, A C, Neubig, R R
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.12.1994
• Subjects: Adrenergic alpha-Antagonists - metabolism; Animals; Binding, Competitive; CHO Cells; Cricetinae; Dibenzazepines - metabolism; Humans; Imidazoles - metabolism; Indoles - metabolism; Isoindoles; Quinolizines - metabolism; Radioligand Assay; Receptors, Adrenergic, alpha-2 - classification; Receptors, Adrenergic, alpha-2 - metabolism
• ISSN: 0022-3565; 1521-0103

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.