G_o/z-biased coupling profile of the dopamine D3 receptor.

ABSTRACT: Dopamine receptors are G protein coupled receptors (GPCRs) that serve as key targets for FDA-approved drugs used to treat various neuropsychiatric disorders. Notably, ~11% of all marketed GPCR-targeting drugs act on dopamine receptors. Five GPCRs mediate the effects of endogenous dopamine and compounds used to treat Parkinson's disease, schizophrenia, and other conditions. However, on-target side effects associated with these medications highlight the need to analyze dopamine receptor signaling to design safer, more effective therapeutics. We characterized the G protein coupling of dopamine D2-like receptors and observed the striking inability of D3R to engage with G_i proteins while effectively activating G_o and G_z subtypes. Applying orthogonal cell-based a

SUBMITTER: Zanetti L 

PROVIDER: S-EPMC12363792 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature