Significant Species Differences in Intestinal Phosphate Absorption between Dogs, Rats, and Monkeys
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- ICHIDA Yasuhiro
- Research Division, Chugai Pharmaceutical Co., Ltd.
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- HOSOKAWA Naoto
- Research Division, Chugai Pharmaceutical Co., Ltd.
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- TAKEMOTO Ryushi
- Chugai Research Institute for Medical Science, Inc.
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- KOIKE Takafumi
- Chugai Research Institute for Medical Science, Inc.
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- NAKATOGAWA Tasuku
- Chugai Research Institute for Medical Science, Inc.
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- HIRANUMA Mayumi
- Chugai Research Institute for Medical Science, Inc.
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- ARAKAWA Hitoshi
- Chugai Research Institute for Medical Science, Inc.
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- MIURA Yukihito
- Chugai Research Institute for Medical Science, Inc.
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- AZABU Hiroko
- Chugai Research Institute for Medical Science, Inc.
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- OHTOMO Shuichi
- Research Division, Chugai Pharmaceutical Co., Ltd.
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- HORIBA Naoshi
- Research Division, Chugai Pharmaceutical Co., Ltd.
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Abstract
<p>A treatment for hyperphosphatemia would be expected to reduce mortality rates for CKD and dialysis patients. Although rodent studies have suggested sodium-dependent phosphate transporter type IIb (NaPi-IIb) as a potential target for hyperphosphatemia, NaPi-IIb selective inhibitors failed to achieve efficacy in human clinical trials. In this study, we analyzed phosphate metabolism in rats, dogs, and monkeys to confirm the species differences. Factors related to phosphate metabolism were measured and intestinal phosphate absorption rate was calculated from fecal excretion in each species. Phosphate uptake by intestinal brush border membrane vesicles (BBMV) and the mRNA expression of NaPi-IIb, PiT-1, and PiT-2 were analyzed. In addition, alkaline phosphatase (ALP) activity was evaluated. The intestinal phosphate absorption rate, including phosphate uptake by BBMV and NaPi-IIb expression, was the highest in dogs. Notably, urinary phosphate excretion was the lowest in monkeys, and their intestinal phosphate absorption rate was by far the lowest. Dogs and rats showed positive correlations between Vmax/Km of phosphate uptake in BBMV and NaPi-IIb expression. Although phosphate uptake was observed in the BBMV of monkeys, NaPi-IIb expression was not detected and ALP activity was low. This study revealed significant species differences in intestinal phosphate absorption. NaPi-IIb contributes to intestinal phosphate uptake in rats and dogs. However, in monkeys, phosphate is poorly absorbed due to the slight degradation of organic phosphate in the intestine.</p>
Journal
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- Journal of Nutritional Science and Vitaminology
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Journal of Nutritional Science and Vitaminology 66 (1), 60-67, 2020-02-29
Center for Academic Publications Japan
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Details 詳細情報について
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- CRID
- 1390565134832031872
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- NII Article ID
- 130007803592
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- NII Book ID
- AA00703822
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- ISSN
- 18817742
- 03014800
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- NDL BIB ID
- 030277225
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- PubMed
- 32115455
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed