ArticleAmerican journal of physiology. Renal physiology2008
TRPV4 mediates hypotonicity-induced ATP release by the thick ascending limb.
Article in American journal of physiology. Renal physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- ROS-Dependent Lipid Peroxidation and Reliant Antioxidant Ferroptosis-Suppressor-Protein 1 in Rheumatoid Arthritis: a Covert Clue for Potential Therapy.Inflammation · 2021Pooled it
- TRPV4: Cell type-specific activation, regulation and function in the vertebrate eye.Current topics in membranes · 2022Article
- TRPV4: A Physio and Pathophysiologically Significant Ion Channel.International journal of molecular sciences · 2020Review
- Stretch-Induced Increases in Intracellular Ca Stimulate Thick Ascending Limb OHypertension (Dallas, Tex. : 1979) · 2020Article
- Extracellular Nucleotides and P2 Receptors in Renal Function.Physiological reviews · 2020Review
- TRPV4 channels contribute to renal myogenic autoregulation in neonatal pigs.American journal of physiology. Renal physiology · 2017Article
- Cell culture: complications due to mechanical release of ATP and activation of purinoceptors.Cell and tissue research · 2017Review
- Calcium-permeable ion channels in the kidney.American journal of physiology. Renal physiology · 2016Review
- TRPV4 mediates flow-induced increases in intracellular Ca in medullary thick ascending limbs.Acta physiologica (Oxford, England) · 2015Article
- Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron.American journal of physiology. Renal physiology · 2015Review
- Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension.American journal of physiology. Renal physiology · 2015Review
- TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb.American journal of physiology. Renal physiology · 2014Article
- Purinergic signalling in the kidney in health and disease.Purinergic signalling · 2014Review
- Novel insights into TRPV4 function in the kidney.Pflugers Archiv : European journal of physiology · 2013Review
- Medullary thick ascending limb buffer vasoconstriction of renal outer-medullary vasa recta in salt-resistant but not salt-sensitive rats.Hypertension (Dallas, Tex. : 1979) · 2012Article
- Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4.American journal of physiology. Cell physiology · 2012Article
- Vesicular and conductive mechanisms of nucleotide release.Purinergic signalling · 2012Review
- ATP mediates flow-induced NO production in thick ascending limbs.American journal of physiology. Renal physiology · 2012Article
- TRPV4 in porcine lens epithelium regulates hemichannel-mediated ATP release and Na-K-ATPase activity.American journal of physiology. Cell physiology · 2012Article
- Calcium regulation by thermo- and osmosensing transient receptor potential vanilloid channels (TRPVs) in human conjunctival epithelial cells.Histochemistry and cell biology · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular ATP is an autocrine/paracrine factor that regulates renal function. Transient receptor potential vanilloid (TRPV) 4 is a cation channel that mediates release of autocrine/paracrine factors by acting as an osmosensor. The renal medulla, and therefore the thick ascending limb, is exposed to osmotic stress. We hypothesize that reduced osmolality stimulates ATP release from the thick ascending limb via transient receptor potential vanilloid (TRPV) 4 activation. We measured ATP release by medullary thick ascending limb suspensions after reducing bath osmolality from 350 to 323 mosmol/kgH2O, using the luciferin-luciferase assay. Decreasing osmolality stimulated ATP release compared with control (38.9+/-7.2 vs. 2.4+/-1.0 pmol/mg protein; n=6, P<0.01). To examine the role of TRPV4, we used 1) Ca-free solutions, 2) a TRPV4 inhibitor, 3) small interfering (si) RNA against TRPV4, and 4) a TRPV4 activator. Removal of Ca completely blocked osmolality-induced ATP release (42.2+/-5.9 vs. 2.6+/-1.5 pmol/mg protein; n=6, P<0.01). In the presence of the TRPV4-selective inhibitor ruthenium red, osmolality-induced ATP release was blocked by 73% (56.4+/-19.9 vs. 8.8+/-2.3 pmol/mg protein; n=6; P<0.03). In vivo treatment of thick ascending limbs with siRNA against TRPV4 decreased osmolality-induced ATP release by 62% (31.5+/-3.4 vs. 12.4+/-1.1 pmol/mg protein; n=6; P<0.01), while reducing TRPV4 expression by 74% compared with the nontreated kidney. Treatment with scrambled siRNA did not affect TRPV4 expression and/or osmolality-induced ATP release. Finally, in the absence of changes in osmolality, the specific TRPV4 agonist 4alpha-PDD increased ATP release (3.6+/-0.9 vs. 25.4+/-7.4 pmol/mg protein; n=6; P<0.04). We concluded that decreases in osmolality stimulate ATP release by thick ascending limbs and this effect is mediated by TRPV4 activation.
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