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Updated: May 21, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
Characterization of Gαs and Gαolf activation by catechol and non-catechol dopamine D1 receptor agonists
Anh Minh Nguyen1, Ana Semeano1, Vianna Quach1
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Bouvé College of Health Sciences, Center for Drug Discovery, Northeastern University, Boston, MA, USA.
Abstract:
The dopamine D1 receptor (D1R) couples to Gαs and Gαolf and is crucial in regulating neurological and neuropsychiatric functions. In the brain, Gαolf is predominantly found in the striatum whereas Gαs is expressed elsewhere. Our in vitro assays revealed that the tetracyclic catechol agonists dihydrexidine, methyl-dihydrexidine, doxanthrine, and the non-catechol compounds PF-8294, PF-6142 exerted full agonism for Gαs coupling but only partial agonism for Gαolf coupling. In contrast, the non-catechol agonist tavapadon acted as a full agonist at Gαolf and a partial agonist at Gαs. The effects of these ligands on the thalamocortical and striatonigral electrophysiological events, as well as on the locomotor activity and cognitive function of mice agreed with their selectivity profiles in vitro. These findings suggest the possibility of achieving region-specific pharmacology and open new directions for developing D1R drugs to treat relevant neurological and neuropsychiatric disorders.
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