ArticleProceedings of the National Academy of Sciences of the United States of America2000
G protein-coupled receptors regulate Na+,K+-ATPase activity and endocytosis by modulating the recruitment of adaptor protein 2 and clathrin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 74 citations in OpenAlex.
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- The zinc receptor, ZnR/GPR39, modulates taste sensitivity by regulating ion secretion in mouse salivary gland.iScience · 2025Article
- Osmoregulatory strategies of estuarine fish Scatophagus argus in response to environmental salinity changes.BMC genomics · 2022Article
- Melatonin integrates multidimensional regulation of NaFrontiers in physiology · 2022Article
- The inositol pyrophosphate 5-InsPScience advances · 2020Article
- Aminopeptidases in Cardiovascular and Renal Function. Role as Predictive Renal Injury Biomarkers.International journal of molecular sciences · 2020Review
- Control of cardiac contraction by sodium: Promises, reckonings, and new beginnings.Cell calcium · 2020Review
- High CO2 Leads to Na,K-ATPase Endocytosis via c-Jun Amino-Terminal Kinase-Induced LMO7b Phosphorylation.Molecular and cellular biology · 2015Article
- Renal proximal tubule Na,K-ATPase is controlled by CREB-regulated transcriptional coactivators as well as salt-inducible kinase 1.Cellular signalling · 2015Article
- Inhibition of epidermal growth factor signaling by the cardiac glycoside ouabain in medulloblastoma.Cancer medicine · 2014Article
- Redox control of cardiac excitability.Antioxidants & redox signaling · 2013Review
- Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Dopamine regulation of Na+-K+-ATPase requires the PDZ-2 domain of sodium hydrogen regulatory factor-1 (NHERF-1) in opossum kidney cells.American journal of physiology. Cell physiology · 2011Article
- Targeting of renal proximal tubule Na,K-ATPase by salt-inducible kinase.Biochemical and biophysical research communications · 2010Review
- Pals-associated tight junction protein functionally links dopamine and angiotensin II to the regulation of sodium transport in renal epithelial cells.British journal of pharmacology · 2009Article
- SIK1/SOS2 networks: decoding sodium signals via calcium-responsive protein kinase pathways.Pflugers Archiv : European journal of physiology · 2009Review
- Reciprocal modulation of function between the D1 and D2 dopamine receptors and the Na+,K+-ATPase.The Journal of biological chemistry · 2008Article
- SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Localization of intracellular compartments that exchange Na,K-ATPase molecules with the plasma membrane in a hormone-dependent manner.British journal of pharmacology · 2007Article
- Genetics of arterial hypertension and hypotension.Naunyn-Schmiedeberg's archives of pharmacology · 2007Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Inhibition of Na(+),K(+)-ATPase (NKA) activity in renal epithelial cells by activation of G protein-coupled receptors is mediated by phosphorylation of the catalytic alpha-subunit followed by endocytosis of active molecules. We examined whether agonists that counteract this effect do so by dephosphorylation of the alpha-subunit or by preventing its internalization through a direct interaction with the endocytic network. Oxymetazoline counteracted the action of dopamine on NKA activity, and this effect was achieved not by preventing alpha-subunit phosphorylation, but by impaired endocytosis of alpha-subunits into clathrin vesicles and early and late endosomes. Dopamine-induced inhibition of NKA activity and alpha-subunit endocytosis required the interaction of adaptor protein 2 (AP-2) with the catalytic alpha-subunit. Phosphorylation of the alpha-subunit is essential because dopamine failed to promote such interaction in cells lacking the protein kinase C phosphorylation residue (S18A). Confocal microscopy confirmed that oxymetazoline prevents incorporation of NKA molecules into clathrin vesicles by inhibiting the ability of dopamine to recruit clathrin to the plasma membrane. Dopamine decreased the basal levels of inositol hexakisphosphate (InsP(6)), whereas oxymetazoline prevented this effect. Similar increments (above basal) in the concentration of InsP(6) induced by oxymetazoline prevented AP-2 binding to the NKA alpha-subunit in response to dopamine. In conclusion, inhibition of NKA activity can be reversed by preventing its endocytosis without altering the state of alpha-subunit phosphorylation; increased InsP(6) in response to G protein-coupled receptor signals blocks the recruitment of AP-2 and thereby clathrin-dependent endocytosis of NKA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.