Fig. 4.

TRPV1-mediated calcium influx regulates MOR1 phosphorylation via GRK5. (A) Basal conditions. (B) Opioids alone activate both G protein signaling and induce MOR1 phosphorylation. MOR1 phosphorylation subsequently initiates β-arrestin recruitment, leading to MOR1 internalization. (C) Calcium influx after TRPV1 activation causes Ca²⁺/CaM binding of GRK5 and translocation to the nucleus. (D) TRPV1 activation before opioid treatment blocks MOR1 phosphorylation. This prevents β-arrestin from internalizing MOR1, but allows G protein signaling.