Effects of pharmacological inhibition of the sodium‐dependent phosphate cotransporter 2b (NPT2b) on intestinal phosphate absorption in mouse and rat models

Autor: Xiaojun Wang, Yanping Xu, Xiaohong Yu, Asim Dey, Hong Y. Zhang, Charity M. Zink, Derek Wodka, Gina Porter, William F. Matter, Leah Porras, Charles A. Reidy, Jeffrey A. Peterson, Brian E. Mattioni, Joseph V. Haas, Mark C. Kowala, John R. Wetterau
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmacology Research & Perspectives, Vol 10, Iss 2, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2052-1707
DOI: 10.1002/prp2.938
Popis: Abstract An excess phosphate burden in renal disease has pathological consequences for bone, kidney, and heart. Therapies to decrease intestinal phosphate absorption have been used to address the problem, but with limited success. Here, we describe the in vivo effects of a novel potent inhibitor of the intestinal sodium‐dependent phosphate cotransporter NPT2b, LY3358966. Following treatment with LY3358966, phosphate uptake into plasma 15 min following an oral dose of radiolabeled phosphate was decreased 74% and 22% in mice and rats, respectively, indicating NPT2b plays a much more dominant role in mice than rats. Following the treatment with LY3358966 and radiolabeled phosphate, mouse feces were collected for 48 h to determine the ability of LY3358966 to inhibit phosphate absorption. Compared to vehicle‐treated animals, there was a significant increase in radiolabeled phosphate recovered in feces (8.6% of the dose, p
Databáze: Directory of Open Access Journals
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