To investigate the effects of β-AR signaling on fibroblast-like synoviocytes (FLS) from adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on β-AR desensitization mediated by GRK2 and β-arrestin2.
In addition, to the actions of βARKct expression on β2- AR signaling, pharmacologic inhibition of GRK2 also increased β2-AR signaling in nonengineered CPCs (lacking βARKct) but had limited effects in βARKct engineered CPCs providing evidence for the strength of the βARKct in inhibiting GRK2 in these cells.
Finally beta-AR signalling is strongly regulated by members of the G-protein-coupled receptor kinase family (GRKs), the best known of which is beta-adrenergic receptor kinase 1 (beta-ARK1). beta-ARK1 mRNA, protein level and enzymatic activity is increased in heart disease, further contributing to an attenuation in beta-AR signalling.