Fig. 9.

A proposed model for CCh and pilocarpine (Pilo) action via M3R. When either CCh (or other agonists such as acetylcholine and Oxo-M) or Pilo bind to M3R, the receptor assumes two similar but distinct conformations. The CCh-bound M3R is able to activate Gq, leading to stimulation of PLCβ and subsequent signaling cascade steps. It also activates β-arrestin–mediated signaling cascade, leading to stimulation of ERK1/2. In contrast, the Pilo-bound M3R conformation is unfavorable for Gq activation. In fact, by competing with CCh, Pilo can antagonize the Gq-dependent signaling cascade; however, Piloc is still able to activate β-arrestin-dependent signaling that leads to ERK1/2 phosphorylation.