ArticleKidney international2008
Effects of the renal medullary pH and ionic environment on vasopressin binding and signaling.
Article in Kidney international, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors.Nature reviews. Nephrology · 2024Review
- Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Urease is an essential component of the acid response network of Staphylococcus aureus and is required for a persistent murine kidney infection.PLoS pathogens · 2019Article
- Therapeutic Targeting of Endosomal G-Protein-Coupled Receptors.Trends in pharmacological sciences · 2018Review
- Molecular mechanisms regulating aquaporin-2 in kidney collecting duct.American journal of physiology. Renal physiology · 2016Review
- Low pH of interstitial fluid around hippocampus of the brain in diabetic OLETF rats.Molecular and cellular therapies · 2014Article
- Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin.The Journal of biological chemistry · 2013Article
- Article
- Simvastatin protects bladder and renal functions following spinal cord injury in rats.Journal of inflammation (London, England) · 2010Article
- The epidermal Ca(2+) gradient: Measurement using the phasor representation of fluorescent lifetime imaging.Biophysical journal · 2010Article
- Angiotensin II and hypertonicity modulate proximal tubular aquaporin 1 expression.American journal of physiology. Renal physiology · 2009Article
- Sensing, signaling and sorting events in kidney epithelial cell physiology.Traffic (Copenhagen, Denmark) · 2009Review
- Loss of bound zinc facilitates amyloid fibril formation of leukocyte-cell-derived chemotaxin 2 (LECT2).The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The kidney has a cortico-medullary interstitial gradient of decreasing pH and increasing concentrations of sodium chloride and urea, but the influence of these gradients on receptor signaling is largely unknown. Here, we measured G-protein coupled receptor function in LLC-PK1 cells acutely exposed to conditions mimicking different kidney regions. Signaling through the parathyroid hormone receptor, normally expressed in the cortex, was greatly reduced at an acidic pH similar to that of the inner medulla. Parathyroid hormone receptor, tagged with green fluorescent protein, showed no ligand-induced internalization. In contrast, under both acidic and hyperosmotic conditions, vasopressin increased intracellular cAMP, and upon binding to its type 2 receptor (V2R) was internalized and degraded. Dose-displacement binding assays with selective vasopressin/oxytocin receptor ligands under inner medullary conditions indicated a shift in the V2R pharmacological profile. Oxytocin did not bind to the V2R, as it does under normal conditions and the vasopressin type 1 receptor (V1R) had reduced affinity for vasopressin compared to the V2R in low pH and high osmolality. We suggest that the cortico-medullary gradient causes a receptor-specific selectivity in ligand binding that is of functional significance to the kidney. While the gradient is important for urinary concentration, it may also play a substantial role in fine-tuning of the vasopressin response through the V2R.
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Registered trials
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.