FIGURE 2.

Dopamine receptors and signaling pathways in neuroimmune network. Simplified schematic representation of DA acting via DRD1‐ and DRD2‐like receptors by G protein‐dependent, by stimulatory (Gαs) or inhibitory Gαi/o subunits, or by G protein‐independent β‐arrestin‐2 (βArr2)‐dependent pathway (for details, see the text). DA binding to DRD1‐like receptor subtypes can elicit two transduction pathways, of which one is coupled to Gαs/olf, driving adenylyl cyclase increasing cyclic adenosine monophosphate (cAMP) activity. In addition to DRD1 effects on cAMP‐regulated signaling, DRD1Rs couple to Gαq to modulate phospholipase C (PLC) pathway, in turn activating phospholipid turnover and increasing diacylglycerol (DAG), releasing Ca2+ from internal stores, and activating protein kinase C (PKC). D2‐like receptor subtypes, coupled to Gαi/o, suppress cAMP activity, thereby producing an inhibitory effect upon DA binding. The G protein‐independent D2R signaling is represented by βArr2‐mediated signaling. The activation of the D2‐like receptors contributes to the constitution of a protein complex composed of protein phosphatase 2A (PP2A), serine/threonine kinase (Akt), and βArr2, where PP2A increases the dephosphorylation and inactivation of Akt, leading to the modulation of glycogen synthase kinase‐3 (GSK‐3) activation