We previously identified that co‐activation of a Gq‐linked heteromeric D1‐D2 dopamine receptor signaling complex results in phospholipase C (PLC)‐dependent intracellular Ca2+ release. We have demonstrated agonist specificity for the D1‐D2 triggered Ca2+ signal and the D1 stimulated cyclic AMP production with three D1 agonists, SKF83959, SKF81297, and SKF83822 that differentially activate either the adenylate cyclase (AC) or PLC pathway. Because the three agonists can activate different signaling pathways, we propose that they are effective pharmacological tools for assessing the mechanisms regulating the D1‐D2 signaling complex. Pretreatment of D1‐D2 expressing cells with each agonist lead to 60% desensitization of the Ca2+ signal within 5 minutes. Intriguingly, occupancy of the D1 binding pocket by SKF 83822 that could not activate the D1‐D2 complex still permitted desensitization of the Ca2+ response. Results from co‐application of the agonists with a D1 or D2 specific antagonist, suggest the desensitization elicited by each agonist is through selective occupancy of the D1 receptor. Furthermore, over‐expression of wild type G‐protein receptor kinase 2 (GRK2) and its catalytically inert construct, but not its regulator of G‐protein signaling (RGS) domain impaired construct, decreased the Ca2+ signal, suggesting the RGS domain of GRK2 is involved in regulating the D1‐D2 receptor signaling cascade.This work is supported by the NIH National Institute on Drug Abuse