Characterization of Gα_s and Gα_olf activation by catechol and non-catechol dopamine D1 receptor agonists.

ABSTRACT: The dopamine D1 receptor (D1R) couples to Gα_s and Gα_olf and is crucial in regulating neurological and neuropsychiatric functions. In the brain, Gα_olf is predominantly found in the striatum whereas Gα_s 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 Gα_s coupling but only partial agonism for Gα_olf coupling. In contrast, the non-catechol agonist tavapadon acted as a full agonist at Gα_olf and a partial agonist at Gα_s. The effects of these ligands on the thalamocortical and striatonigral electrophysiological events, as well as on the loc

SUBMITTER: Nguyen AM 

PROVIDER: S-EPMC12084000 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature