A comparison of agonist-specific coupling of cloned human alpha(2)-adrenoceptor subtypes.

The Babraham Institute Laboratory of Receptor Signalling, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ.

British journal of pharmacology 2000 Nov

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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.

Citation

J E Rudling, J Richardson, P D Evans. A comparison of agonist-specific coupling of cloned human alpha(2)-adrenoceptor subtypes. British journal of pharmacology. 2000 Nov;131(5):933-41