Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms

A. Dopamine D1 and D2 receptor homooligomers modulate adenylyl cyclase activity and cAMP accumulation in opposite ways through Gs/olf and Gi/o proteins, respectively (left panel). D1–D2 receptor heteromer activation leads to a novel signaling pathway mediated through Gq/11 protein activation, to a rapid, transient, intracellular calcium mobilization from endoplasmic reticulum (right panel). This calcium signal involves phospholipase C (PLC) and inositol-triphosphate (IP3) receptors and leads to CaMKIIα activation.B. Activation of dopamine D5 receptor homooligomers results in the mobilization of intracellular calcium involving Gq/11 and PLC activation, and extracellular calcium influx leading to a robust rise in intracellular calcium (left panel). D5-D2 receptor heteromer formation confers two roles to D2 receptor, one is the inhibition exerted by D2R on D5R-induced rise in calcium when only D5 receptor is activated (middle panel), and the ability of D2R to participate in the increase in calcium mobilization when both D5 and D2 receptors forming the heteromer are co-stimulated (right panel)

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Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms. () Ahmed Hasbi, et al. Curr Opin Pharmacol. ;10(1):93. Figure: F1. All organisms Mus musculus Homo sapiens Drosophila melanogaster

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