Significant Species Differences in Intestinal Phosphate Absorption between Dogs, Rats, and Monkeys

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...

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Published in:	Journal of Nutritional Science and Vitaminology Vol. 66; no. 1; pp. 60 - 67
Main Authors:	ICHIDA, Yasuhiro, HOSOKAWA, Naoto, TAKEMOTO, Ryushi, KOIKE, Takafumi, NAKATOGAWA, Tasuku, HIRANUMA, Mayumi, ARAKAWA, Hitoshi, MIURA, Yukihito, AZABU, Hiroko, OHTOMO, Shuichi, HORIBA, Naoshi
Format:	Journal Article
Language:	English
Published:	Japan Center for Academic Publications Japan 29-02-2020
Subjects:	Alkaline Phosphatase - metabolism Animals BBMV Dogs Haplorhini Intestinal Absorption - physiology Microvilli - metabolism NaPi-IIb Phosphates - metabolism PiT-1 PiT-2 Rats Sodium-Phosphate Cotransporter Proteins, Type IIb - analysis Sodium-Phosphate Cotransporter Proteins, Type IIb - genetics Sodium-Phosphate Cotransporter Proteins, Type IIb - metabolism Species Specificity uptake NaPi-IIb PiT-2 uptake BBMV PiT-1
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Summary:	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.
ISSN:	0301-4800 1881-7742
DOI:	10.3177/jnsv.66.60