Skip to main content
. 2022 Aug 17;13:947785. doi: 10.3389/fphar.2022.947785

FIGURE 3.

FIGURE 3

Schematic diagram of the dopamine receptor complex signaling cascade. D1-D2 heterodimers induce calcium release via a Gαq-dependent pathway, distinct from Gs/Golf- or Gi/Go- dependent pathways activated by D1 receptor heterodimers or D2 receptor heterodimers. D1-D2 heterodimers trigger calcium signaling by activating Gαq and PLC, leading to the activation of calmodulin kinase II-α(CaMKIIα). When calcium ions enter cells through various ion channels on the membrane, CaMKIIα is activated. Activation of CaMKIIα promotes its autophosphorylation, which binds to GluN2B and phosphorylates GluN2B at the S1303 site (p-GluN2B). Studies have shown that the interaction between GluN2B and CaMKIIα is significant for the synaptic CaMKIIα localization and activity. Phosphorylation of GluA1 and GluN2B plays a key role in the glutamatergic transmission and is regulated by the D1-D2 heterodimers signaling pathway. Inhibition of the recruitment, deletion, or activity of Ca(2+)-permeable AMPA receptors (CP-AMPARs) would interfere with long-term depression. CaMKIIα/BDNF/CREB-dependent neural plasticity pathways may be an important target for dopamine receptor complex research. D1R, dopamine D1-like receptor; D2R, dopamine D2-like receptor; PLC, Phospholipase C; IP3, Inositol triphosphate; CamKII, Calmodulin kinase II; p-CamKII, Phosphorylated CamKII; GluA1, glutamate A1; GluN2B, Glutamate Receptor Ionotropic, NMDA 2B; CP-AMPARs, calcium-permeable AMPA receptors; AC, Adenylyl cyclase; cAMP, cyclic adenosine monophosphate; CREB, cAMP-response element-binding protein; p-CREB, Phosphorylated-CREB; BDNF, Brain-Derived Neurotrophic Factor.