ArticleAmerican journal of physiology. Renal physiology2012
Calmodulin-sensitive adenylyl cyclases mediate AVP-dependent cAMP production and Cl- secretion by human autosomal dominant polycystic kidney cells.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Lack of ANKMY2 suppresses kidney cystogenesis in embryonic- and adult-onset polycystic kidney disease.PLoS genetics · 2025Article
- Kcnn4/KCa3.1 inhibition blunts polycystic kidney disease progression in mouse models.JCI insight · 2025Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Review
- Hyperosmolality activates polycystin-2 and TRPM4 in renal primary cilium.Pflugers Archiv : European journal of physiology · 2025Article
- Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression.Life (Basel, Switzerland) · 2023Article
- Regenerative Calcium Currents in Renal Primary Cilia.Frontiers in physiology · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.Nature reviews. Nephrology · 2021Review
- Modeling Neoplastic Growth in Renal Cell Carcinoma and Polycystic Kidney Disease.International journal of molecular sciences · 2021Review
- The Biology of Vasopressin.Biomedicines · 2021Review
- Modulation of polycystic kidney disease by G-protein coupled receptors and cyclic AMP signaling.Cellular signalling · 2020Review
- The pathobiology of polycystic kidney disease from a metabolic viewpoint.Nature reviews. Nephrology · 2019Review
- Fundamental insights into autosomal dominant polycystic kidney disease from human-based cell models.Pediatric nephrology (Berlin, Germany) · 2019Article
- Simple renal cysts are associated with increased arterial stiffness in a Taiwanese population.Hypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Polycystin 2 regulates mitochondrial CaScience signaling · 2019Article
- Activation of Calcium-Sensing Receptor increases intracellular calcium and decreases cAMP and mTOR in PKD1 deficient cells.Scientific reports · 2018Article
- Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease.Kidney international · 2018Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In autosomal dominant polycystic kidney disease (ADPKD), binding of AVP to the V2 receptor (V2R) increases cAMP and accelerates cyst growth by stimulating cell proliferation and Cl(-)-dependent fluid secretion. Basal cAMP is elevated in human ADPKD cells compared with normal human kidney (NHK) cells. V2R mRNA levels are elevated in ADPKD cells; however, AVP caused a greater increase in global cAMP in NHK cells, suggesting an intrinsic difference in cAMP regulation. Expression, regulatory properties, and receptor coupling of specific adenylyl cyclases (ACs) provide temporal and spatial regulation of the cAMP signal. ADPKD and NHK cells express mRNAs for all nine ACs. Ca(2+)-inhibited ACs 5 and 6 are increased in ADPKD cells, while Ca(2+)/CaM-stimulated ACs 1 and 3 are downregulated. ACs 1, 3, 5, and 6 were detected in cyst cells in situ, and codistribution with aquaporin-2 suggests that these cysts were derived from collecting ducts. To determine the contribution of CaM-sensitive ACs to AVP signaling, cells were treated with W-7, a CaM inhibitor. W-7 decreased AVP-induced cAMP production and Cl(-) secretion by ADPKD cells. CaMKII inhibition increased AVP-induced cAMP, suggesting that cAMP synthesis is mediated by AC3. In contrast, CaM and CaMKII inhibition in NHK cells did not affect AVP-induced cAMP production. Restriction of intracellular Ca(2+) switched the response in NHK cells, such that CaM inhibition decreased AVP-induced cAMP production. We suggest that a compensatory response to decreased Ca(2+) in ADPKD cells switches V2R coupling from Ca(2+)-inhibited ACs 5/6 to Ca(2+)/CaM-stimulated AC3, to mitigate high cAMP levels in response to continuous AVP stimulation.
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