ArticleHypertension (Dallas, Tex. : 1979)2010
HK-2 human renal proximal tubule cells as a model for G protein-coupled receptor kinase type 4-mediated dopamine 1 receptor uncoupling.
Article in Hypertension (Dallas, Tex. : 1979), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
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- The Interplay between von Hippel-Lindau Tumor Suppressor Gene, Lon Protease, ROS Accumulation, and Inflammation in Clear Cell Renal Cell Carcinoma.Current issues in molecular biology · 2024Article
- The Rise in Tubular pH during Hypercalciuria Exacerbates Calcium Stone Formation.International journal of molecular sciences · 2024Article
- Cysteine conjugates of acetaminophen and p-aminophenol are potent inducers of cellular impairment in human proximal tubular kidney HK-2 cells.Archives of toxicology · 2023Article
- Delivery and Transcriptome Assessment of an In Vitro Three-Dimensional Proximal Tubule Model Established by Human Kidney 2 Cells in Clinical Gelatin Sponges.International journal of molecular sciences · 2023Article
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
- Impact of cytotoxic agents or apoptosis stimulants on αklotho in MDCK, NRK-52E and HK2 kidney cells.Aging · 2022Article
- Epithelial Sodium Channel Alpha Subunit (αENaC) Is Associated with Inverse Salt Sensitivity of Blood Pressure.Biomedicines · 2022Article
- GRK4, A Potential Link between Hypertension and Breast Cancer.Journal of cell science & therapy · 2022Article
- Potential and Limits of Kidney Cells for Evaluation of Renal Excretion.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Dopamine DHypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model.International journal of molecular sciences · 2020Article
- The Dopamine DHypertension (Dallas, Tex. : 1979) · 2019Article
- RNAa and Vector-Mediated Overexpression of DIRAS1 Suppresses Tumor Growth and Migration in Renal Cell Carcinoma.Molecular therapy. Nucleic acids · 2018Article
- The Synergistic Roles of Cholecystokinin B and Dopamine D5 Receptors on the Regulation of Renal Sodium Excretion.PloS one · 2016Article
- Exosomal transfer from human renal proximal tubule cells to distal tubule and collecting duct cells.Clinical biochemistry · 2014Article
- The cooperative roles of the dopamine receptors, D1R and D5R, on the regulation of renal sodium transport.Kidney international · 2014Article
- Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells.Redox biology · 2014Article
- Human kidney-2 cells harbor functional dopamine D1 receptors that require Giα for Gq/11α signaling.American journal of physiology. Renal physiology · 2013Article
- A linear relationship between the ex-vivo sodium mediated expression of two sodium regulatory pathways as a surrogate marker of salt sensitivity of blood pressure in exfoliated human renal proximal tubule cells: the virtual renal biopsy.Clinica chimica acta; international journal of clinical chemistry · 2013Article
Corrections and comments
- Erratum issuedJones, John E [added]
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
HK-2 human renal proximal tubule cells (RPTC) are commonly used in the in vitro study of "normal" RPTCs. We discovered recently that HK-2 cells are uncoupled from dopamine 1 receptor (D(1)R) adenylyl cyclase (AC) stimulation. We hypothesized that G protein-coupled receptor kinase type 4 (GRK4) single nucleotide polymorphisms may be responsible for the D(1)R/AC uncoupling in HK-2. This hypothesis was tested by genotyping GRK4 single nucleotide polymorphisms, measuring D(1)-like receptor agonist (fenoldopam)-stimulated cAMP accumulation, quantifying D(1)R inhibition of sodium transport, and testing the ability of GRK4 small interfering RNA to reverse the D(1)R/AC uncoupling. We compared HK-2 with 2 normally coupled human RPTC cell lines and 2 uncoupled RPTC cell lines. The HK-2 cell line was found to have 4 of 6 potential GRK4 single nucleotide polymorphisms known to uncouple the D(1)R from AC (namely, R65L, A142V, and A486V). AC response to fenoldopam stimulation was increased in the 2 normally coupled human RPTC cell lines (FEN: 2.02+/-0.05-fold and 2.33+/-0.19-fold over control; P<0.001; n=4) but not in the 2 uncoupled or HK-2 cell lines. GRK4 small interfering RNA rescued the fenoldopam-mediated AC stimulation in the uncoupled cells, including HK-2. The expected fenoldopam-mediated inhibition of sodium hydrogen exchanger type 3 was absent in HK-2 (n=6) and uncoupled RPTC cell lines (n=6) but was observed in the 2 normally coupled human RPTC cell lines (-25.41+/-4.7% and -27.36+/-2.70%; P<0.001; n=6), which express wild-type GRK4. Despite the fact that HK-2 cells retain many functional characteristics of RPTCs, they are not normal from the perspective of dopaminergic function.
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