title: A comparison of agonist-specific coupling of cloned human alpha(2)-adrenoceptor subtypes.
abstract: The agonist-specific coupling properties of the three cloned human alpha(2)-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 alpha(2A)-adrenoceptor only to the inhibition of forskolin-stimulated cyclic AMP production. However, meta-octopamine couples the alpha(2B)- and alpha(2C)-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 alpha(2)-adrenoceptor subtypes. The effects of meta-octopamine are around two orders of magnitude less potent than those of noradrenaline on both the alpha(2A)- and alpha(2B)-adrenoceptor subtypes. In contrast, in the case of the alpha(2C)-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 alpha(2C)-adrenoceptors in vivo. The results show that the modulation of cyclic AMP production occurs in both a subtype- and agonist-specific manner for alpha(2A)-adrenoceptors and in a subtype specific manner for alpha(2B)- and alpha(2C)-adrenoceptors.
authors.affiliation: The Babraham Institute Laboratory of Receptor Signalling, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ.
authors.forename: J E
authors.initials: JE
authors.lastname: Rudling
authors.forename: J
authors.initials: J
authors.lastname: Richardson
authors.forename: P D
authors.initials: PD
authors.lastname: Evans
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D009655:Octopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D013329:Structure-Activity Relationship; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D010566:Virulence Factors, Bordetella; D009655:Octopamine; C005310:norfenefrine; D000242:Cyclic AMP; D010741:Phospholipases A; D009638:Norepinephrine