RT Journal Article
SR Electronic
T1 Calcium Signaling by Dopamine D5 Receptor and D5-D2 Receptor Hetero-Oligomers Occurs by a Mechanism Distinct from That for Dopamine D1-D2 Receptor Hetero-Oligomers
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 843
OP 854
DO 10.1124/mol.108.051805
VO 75
IS 4
A1 So, Christopher H.
A1 Verma, Vaneeta
A1 Alijaniaram, Mohammad
A1 Cheng, Regina
A1 Rashid, Asim J.
A1 O'Dowd, Brian F.
A1 George, Susan R.
YR 2009
UL http://molpharm.aspetjournals.org/content/75/4/843.abstract
AB In this report, we investigated whether the D5 dopamine receptor, given its structural and sequence homology with the D1 receptor, could interact with the D2 receptor to mediate a calcium signal similar to the Gq/11 protein-linked phospholipase C-mediated calcium signal resulting from the coactivation of D1 and D2 dopamine receptors within D1-D2 receptor heterooligomers. Fluorescent resonance energy transfer experiments demonstrated close colocalization of cell surface D5 and D2 receptors (<100 Å), indicating hetero-oligomerization of D5 and D2 receptors in cells coexpressing both receptors. Coactivation of D5 and D2 receptors within the D5-D2 hetero-oligomers activated a calcium signal. However, unlike what is observed for D1 receptors, which activate extensive calcium mobilization only within a complex with the D2 receptors, a robust calcium signal was triggered by D5 receptors expressed alone. Hetero-oligomerization with the D2 receptor attenuated the ability of the D5 receptor to trigger a calcium signal. The D5 and D5-D2-associated calcium signals were Gq/11 protein-linked and phospholipase C-mediated but were also critically dependent on the influx of extracellular calcium through store-operated calcium channels, unlike the calcium release triggered by D1-D2 heterooligomers. Collectively, these results demonstrate that calcium signaling through D5-D2 receptor hetero-oligomers occurred through a distinct mechanism to achieve an increase in intracellular calcium levels. The American Society for Pharmacology and Experimental Therapeutics