15265765

pubmed:Citation

5

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 [(3)H]SCH-23390 binding and immunoblotting, that dopamine recruits D(1A) receptors to the plasma membrane in rat renal proximal tubules. Furthermore, radioligand binding and/or immunoblotting experiments using pharmacological modulators showed that dopamine-induced D(1A) receptor recruitment requires activation of cell surface D(1)-like receptors, activation of adenylyl cyclase, and intact endocytic vesicles with internal acidic pH. A key finding of this study was that these recruited D(1A) receptors were functional because they potentiated dopamine-induced [(35)S]GTPgammaS binding, cAMP accumulation, and Na-K-ATPase inhibition. Interestingly, dopamine increased immunoreactivity of D(1A) receptors specifically in caveolin-rich plasma membranes isolated by a sucrose density gradient. In support of this observation, coimmunoprecipitation studies showed that D(1A) receptors interacted with caveolin-2 in an agonist-dependent fashion. The caveolin-rich plasma membranes had a high content of the alpha(1)-subunit of Na-K-ATPase, which is a downstream target of D(1A) receptor signaling in proximal tubules. These results show that dopamine, via the D(1)-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 close proximity to targets such as Na-K-ATPase in proximal tubules of Sprague-Dawley rats.

eng

IM

MEDLINE

1931-857X

Print

NLM

F921-31

pubmed-meshheading:15265765-Animals, pubmed-meshheading:15265765-Benzazepines, pubmed-meshheading:15265765-Blotting, Western, pubmed-meshheading:15265765-Cell Membrane, pubmed-meshheading:15265765-Cyclic AMP, pubmed-meshheading:15265765-Dopamine, pubmed-meshheading:15265765-Dopamine Antagonists, pubmed-meshheading:15265765-Enzyme Inhibitors, pubmed-meshheading:15265765-Forskolin, pubmed-meshheading:15265765-GTP-Binding Proteins, pubmed-meshheading:15265765-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:15265765-Kidney Tubules, Proximal, pubmed-meshheading:15265765-Macrolides, pubmed-meshheading:15265765-Male, pubmed-meshheading:15265765-Microvilli, pubmed-meshheading:15265765-Precipitin Tests, pubmed-meshheading:15265765-Radioligand Assay, pubmed-meshheading:15265765-Rats, pubmed-meshheading:15265765-Rats, Sprague-Dawley, pubmed-meshheading:15265765-Receptors, Dopamine D1, pubmed-meshheading:15265765-Second Messenger Systems, pubmed-meshheading:15265765-Signal Transduction, pubmed-meshheading:15265765-Sodium-Hydrogen Antiporter, pubmed-meshheading:15265765-Sodium-Potassium-Exchanging ATPase

Dopamine recruits D1A receptors to Na-K-ATPase-rich caveolar plasma membranes in rat renal proximal tubules.

Journal Article, Research Support, U.S. Gov't, P.H.S.