Caveolin-1 and dopamine-mediated internalization of nakatpase in human renal proximal tubule cells

John J. Gildea, Jonathan A. Israel, Andrew K. Johnson, Jin Zhang, Pedro A. Jose, Robin A. Felder

Research output: Contribution to journalArticle

Abstract

In moderate sodium-replete states, dopamine 1-like receptors (D1R/D5R) are responsible for regulating >50% of renal sodium excretion. This is partly mediated by internalization and inactivation of NaKATPase, when associated with adapter protein 2. We used dopaminergic stimulation via fenoldopam (D1-like receptor agonist) to study the interaction among D1-like receptors, caveolin-1 (CAV1), and the G protein-coupled receptor kinase type 4 in cultured human renal proximal tubule cells (RPTCs). We compared 2 groups of RPTCs, 1 of cell lines that were isolated from normal subjects (nRPTCs) and a second group of cell lines that have D1-like receptors that are uncoupled (uncoupled RPTCs) from adenylyl cyclase second messengers. In nRPTCs, fenoldopam increased the plasma membrane expression of D1R (10.0-fold) and CAV1 (1.3-fold) and markedly decreased G protein-coupled receptor kinase type 4 by 94±8%; no effects were seen in uncoupled RPTCs. Fenoldopam also increased the association of adapter protein 2 and NaKATPase by 53±9% in nRPTCs but not in uncoupled RPTCs. When CAV1 expression was reduced by 86.0±8.5% using small interfering RNA, restimulation of the D1-like receptors with fenoldopam in nRPTCs resulted in only a 7±9% increase in association between adapter protein 2 and NaKATPase. Basal CAV1 expression and association with G protein-coupled receptor kinase type 4 was decreased in uncoupled RPTCs (58±5% decrease in association) relative to nRPTCs. We conclude that the scaffolding protein CAV1 is necessary for the association of D1-like receptors with G protein-coupled receptor kinase type 4 and the adapter protein 2-associated reduction in plasma membrane NaKATPase.

Original languageEnglish (US)
Pages (from-to)1070-1076
Number of pages7
JournalHypertension
Volume54
Issue number5
DOIs
StatePublished - Nov 2009

Keywords

  • Caveolin
  • Dopamine receptors
  • FRET
  • GRK4
  • Hypertension
  • NaKATPase
  • Proximal tubule

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Gildea, J. J., Israel, J. A., Johnson, A. K., Zhang, J., Jose, P. A., & Felder, R. A. (2009). Caveolin-1 and dopamine-mediated internalization of nakatpase in human renal proximal tubule cells. Hypertension, 54(5), 1070-1076. https://doi.org/10.1161/HYPERTENSIONAHA.109.134338