التفاصيل البيبلوغرافية
| العنوان: |
Inhibition of pannexin‐1 does not restore electrolyte balance in precystic Pkd1 knockout mice. |
| المؤلفون: |
van Megen, Wouter H.1 (AUTHOR), van Houtert, Teun J.1 (AUTHOR), Bos, Caro1 (AUTHOR), Peters, Dorien J. M.2 (AUTHOR), de Baaij, Jeroen H. F.1 (AUTHOR), Hoenderop, Joost G. J.1 (AUTHOR) joost.hoenderop@radboudumc.nl |
| المصدر: |
Physiological Reports. Apr2024, Vol. 12 Issue 7, p1-13. 13p. |
| مصطلحات موضوعية: |
*POLYCYSTIC kidney disease, *WATER-electrolyte balance (Physiology), *KNOCKOUT mice, *GENE silencing, *SODIUM-glucose cotransporters |
| مستخلص: |
Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by the formation of fluid‐filled cysts in the kidney. In a subset of ADPKD patients, reduced blood calcium (Ca2+) and magnesium (Mg2+) concentrations are observed. As cystic fluid contains increased ATP concentrations and purinergic signaling reduces electrolyte reabsorption, we hypothesized that inhibiting ATP release could normalize blood Ca2+ and Mg2+ levels in ADPKD. Inducible kidney‐specific Pkd1 knockout mice (iKsp‐Pkd1−/−) exhibit hypocalcemia and hypomagnesemia in a precystic stage and show increased expression of the ATP‐release channel pannexin‐1. Therefore, we administered the pannexin‐1 inhibitor brilliant blue‐FCF (BB‐FCF) every other day from Day 3 to 28 post‐induction of Pkd1 gene inactivation. On Day 29, both serum Ca2+ and Mg2+ concentrations were reduced in iKsp‐Pkd1−/− mice, while urinary Ca2+ and Mg2+ excretion was similar between the genotypes. However, serum and urinary levels of Ca2+ and Mg2+ were unaltered by BB‐FCF treatment, regardless of genotype. BB‐FCF did significantly decrease gene expression of the ion channels Trpm6 and Trpv5 in both control and iKsp‐Pkd1−/− mice. Finally, no renoprotective effects of BB‐FCF treatment were observed in iKsp‐Pkd1−/− mice. Thus, administration of BB‐FCF failed to normalize serum Ca2+ and Mg2+ levels. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
Full Text Finder