In vivo effects of renal Npt2a inhibition
العنوان: | In vivo effects of renal Npt2a inhibition |
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المؤلفون: | Jessica A Dominguez Rieg, Timo Rieg, Linto Thomas, Jianxiang Xue |
المصدر: | Revista Cubana de Investigaciones Biomédicas, Vol 38, Iss 5 (2020) |
بيانات النشر: | Wiley, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | npt2a inhibitor, mice, urinary phosphate excretion, animal model, mice, lcsh:R5-920, In vivo, Chemistry, Genetics, Pharmacology, lcsh:Medicine (General), Molecular Biology, Biochemistry, Biotechnology |
الوصف: | Introduction: Hyperphosphatemia is common in patients with chronic kidney disease and associated with increased mortality. Oral phosphate binders and dietary phosphate restriction are the current management protocols for patients with hyperphosphatemia; however, their effectiveness is insufficient. In the kidney, the sodium-phosphate cotransporter Npt2a is responsible for bulk uptake of phosphate in the proximal tubule. Recently, an orally bioavailable selective Npt2a inhibitor (Npt2a-I, PF-06869206) has been described to reduce phosphate uptake in HEK cells transfected with mouse or rat Npt2a. So far, its physiological in vivo function has not been tested. Objective: To describe the in vivo effect of renal NPt2a inhibition in C57BL/6J mice Material and Methods: Based on in vitro IC 50 concentrations, we chose to study 30 mg/kg (oral gavage, 1% of body weight) in short-term (3 hours) metabolic cage experiments in C57BL/6J mice. Results: Compared to vehicle (n=14), bolus administration of Npt2a-I (n=12) caused significantly higher (~4-fold) urinary phosphate excretion (104±8 vs 27 ±6 µmol*min -1, P |
تدمد: | 1530-6860 0892-6638 |
DOI: | 10.1096/fasebj.2019.33.1_supplement.751.2 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d56c61fd21f912a0c6dfe99fd0ccfa7 https://doi.org/10.1096/fasebj.2019.33.1_supplement.751.2 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....8d56c61fd21f912a0c6dfe99fd0ccfa7 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15306860 08926638 |
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DOI: | 10.1096/fasebj.2019.33.1_supplement.751.2 |