A comparison of agonist‐specific coupling of cloned human α2‐adrenoceptor subtypes

• Published in: British journal of pharmacology 2000-11, Vol.131 (5), p.933-941
• Main Authors: Rudling, Jane E, Richardson, Jo, Evans, Peter D
• Format: Article
• Language: English
• Subjects: adenylyl cyclase; Biological and medical sciences; Cell receptors; Cell structures and functions; cyclic AMP; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); noradrenaline; octopamine; α2‐Adrenoceptor subtypes
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703644

The agonist‐specific coupling properties of the three cloned human α2‐adrenoceptor subtypes have been compared, when expressed at similar levels in Chinese hamster ovary (CHO) cell lines, using noradrenaline and (±)‐meta‐octopamine as agonists. Noradrenaline can couple the receptor to both the inhibition and stimulation of forskolin‐stimulated cyclic AMP production in all three receptor subtypes, with the relative strength of the coupling to the pathways varying for each of the receptor subtypes. meta‐Octopamine selectively couples the α2A‐adrenoceptor only to the inhibition of forskolin‐stimulated cyclic AMP production. However, meta‐octopamine couples the α2B‐ and α2C‐adrenoceptors to both the inhibition and stimulation of forskolin‐stimulated cyclic AMP production. The relative potency of meta‐octopamine to noradrenaline varies between the different α2‐adrenoceptor subtypes. The effects of meta‐octopamine are around two orders of magnitude less potent than those of noradrenaline on both the α2A‐ and α2B‐adrenoceptor subtypes. In contrast, in the case of the α2C‐adrenoceptor, meta‐octopamine is only one order of magnitude less potent than noradrenaline in the stimulation of forskolin‐stimulated cyclic AMP production and, in addition, is equipotent with noradrenaline in the inhibition of forskolin‐stimulated cyclic AMP production and has an increased maximal response. This raises the possibility that meta‐octopamine may have physiologically important actions via α2C‐adrenoceptors in vivo. The results show that the modulation of cyclic AMP production occurs in both a subtype‐ and agonist‐specific manner for α2A‐adrenoceptors and in a subtype specific manner for α2B‐ and α2C‐adrenoceptors. British Journal of Pharmacology (2000) 131, 933–941; doi:10.1038/sj.bjp.0703644