Activation of dopamine D_1A receptors in renal proximal tubules causes inhibition of sodium transporters (Na,K-ATPase and Na,H-Exchanger) leading to a decrease in sodium reabsorption. In addition to being localized on the plasma membrane, D_1A receptors are mainly present in intracellular compartments under basal conditions. We observed, using [³H] SCH 23390 binding and immunoblotting, that dopamine recruits D_1A receptors to the plasma membrane in rat renal proximal tubules. Further, radioligand binding and/or immunoblotting experiments using pharmacological modulators showed that dopamine-induced D_1A receptor recruitment requires activation of cell surface D₁-like receptors, activation of adenylyl cyclase, and intact endocytic vesicles with internal acidic pH. A key finding of the project was that these recruited D_1A receptors were functional because they potentiated dopamine-induced [³⁵S] GTPS binding, cAMP accumulation, and Na,K-ATPase inhibition. Interestingly, dopamine increased immunoreactivity of D_1A receptors specifically in caveolin-rich plasma membranes isolated by sucrose density gradient. In support of this observation, coimmunoprecipitation studies showed that D_1A receptors interacted with caveolin-2 in agonist-dependent fashion. The caveolin-rich plasma membranes had a high content of a1 subunit of Na,K-ATPase, which is a downstream target of D_1A receptor signaling in proximal tubules. These results show that dopamine, via D₁-like receptor-adenylyl cyclase pathway, recruits D_1A receptors to the plasma membrane. These newly recruited receptors couple to G-proteins, increase cAMP and participate in dopamine-mediated inhibition of Na,K-ATPase in proximal tubules. Moreover, dopamine-induced recruitment of D_1A receptors to the caveolin-rich plasma membranes brings them in a close proximity to targets such as Na,K-ATPase in proximal tubules of Sprague-Dawley rats.