CP-25 inhibits the hyperactivation of rheumatic synoviocytes by suppressing the switch in G_αs-G_αi coupling to the β₂-adrenergic receptor.

ABSTRACT: In essence, the β₂ adrenergic receptor (β₂AR) plays an antiproliferative role by increasing the intracellular cyclic 3',5'-adenosine monophosphate (cAMP) concentration through G_αs coupling, but interestingly, β₂AR antagonists are able to effectively inhibit fibroblast-like synoviocytes (FLSs) proliferation, thus ameliorating experimental RA, indicating that the β₂AR signalling pathway is impaired in RA FLSs via unknown mechanisms. The local epinephrine (Epi) level was found to be much higher in inflammatory joints than in normal joints, and high-level stimulation with Epi or isoproterenol (ISO) directly promoted FLSs proliferation and migration due to impaired β₂AR signalling and cAMP production. By applying inhibitor of rec

SUBMITTER: Ge M 

PROVIDER: S-EPMC10688045 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature