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Review
.2010 Feb;10(1):93-9.
doi: 10.1016/j.coph.2009.09.011. Epub 2009 Nov 10.

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

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Review

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.2010 Feb.

Abstract

The repertoire of signal transduction pathways activated by dopamine in brain includes the increase of intracellular calcium. However the mechanism(s) by which dopamine activated this important second messenger system was/were unknown. Although we showed that activation of the D5 dopamine receptor increased calcium concentrations, the restricted anatomic distribution of this receptor made this unlikely to be the major mechanism in brain. We have identified novel heteromeric dopamine receptor complexes that are linked to calcium signaling. The calcium pathway activated through the D1-D2 receptor heteromer involved coupling to Gq, through phospholipase C and IP(3) receptors to result in a rise in intracellular calcium. The calcium rise activated through the D2-D5 receptor heteromer involved a small rise in intracellular calcium through the Gq pathway that triggered a store-operated channel mediated influx of extracellular calcium. These novel receptor heteromeric complexes, for the first time, establish the link between dopamine action and rapid calcium signaling.

Copyright 2009 Elsevier Ltd. All rights reserved.

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Figures

Figure 1
Figure 1
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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