Antimuscarinic drugs exert β-arrestin-biased agonism at the muscarinic acetylcholine type 1 receptor to promote DRG neuritogenesis - PubMed
6 hours ago
- #neuritogenesis
- #β-arrestin-biased agonism
- #M1 muscarinic receptor
- Antimuscarinic drugs pirenzepine (PZ) and muscarinic toxin 7 (MT7) act as β-arrestin-biased agonists at the M1 muscarinic receptor.
- These drugs promote neuritogenesis in adult rodent dorsal root ganglion sensory neurons via β-arrestin-dependent activation of ERK1/2 signaling.
- Activation occurs in a G protein-independent and receptor internalization-independent manner.
- Phosphorylation at specific M1R residues (Ser251 and Thr254) is crucial for β-arrestin recruitment and ERK activation by PZ and MT7.
- Casein kinase 2 activity is required for the β-arrestin-biased effects, while Gαq, GPCR kinases, and GRKs are not involved.
- Inhibition of CK2 blocks β-arrestin recruitment, ERK activation, and neurite outgrowth induced by PZ in DRG neurons.