Partial agonist activity of (+) 8 – OH – DPAT at human (h)α2B adrenergic receptors
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Institut de Recherche Pierre Fabre Biologie Cellulaire et Moleculaire, France
8 – OH – DPAT [8 – hydroxyl – 2 – (di – n – propylamino) tetralin] is considered as the prototypical agonist at serotonin 5 – HT1A receptors and has been largely used for in vitro and in vivo characterization of 5-HT1A receptor – mediated effects. 8 – OH – DPAT is a racemic mixture of the R (+) and the S (–) isomer, characterized by different functional activities: while the R (+) enantiomer is a near full 5 – HT1A receptor agonist, the S (–) enantiomer exhibits partial agonist activity, both with similar potency.
Besides its actions at the 5 – HT1A receptor, 8 – OH – DPAT possesses affinity for a number of other sites, including 5 – HT7 and α2 adrenergic receptors. Here, we test the drug’s actions at subtypes of recombinant human (h) α2 receptors and report that (+) 8 – OH – DPAT exhibits an about 10 – fold selectivity for the hα2B (Ki about 100 nM) over hα2A and hα2c subtypes. In contrast, the S (–) enantiomer showed similar weak affinities for the three receptor subtypes (Kis about 1.5 – 2.5 µM). The binding affinity of (+) 8 – OH – DPAT at the hα2B receptor was sensitive to guanine nucleotides, indicating agonist properties. Moreover, using [35S]GTPγS binding at CHO – hα2B cell membranes and GIRK current recordings in Xenopus oocytes expressing hα2B, partial agonist activity of (+) 8 – OH – DPAT was confirmed in two different functional assays.
Thus, (+) 8 – OH – DPAT is a partial agonist at hα2B receptors, a property that might contribute to the effects of the compound described in vivo.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
Imaging & Neuroendocrinology
Citation:
Heusler
P
(2009). Partial agonist activity of (+) 8 – OH – DPAT at human (h)α2B adrenergic receptors.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.168
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Received:
26 Nov 2009;
Published Online:
26 Nov 2009.
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Correspondence:
Peter Heusler, Institut de Recherche Pierre Fabre Biologie Cellulaire et Moleculaire, Castres, France, peter.heusler@pierre-fabre.com