Intestinal phosphate absorption is mediated by multiple transport systems in rats

Area of Science:

• Physiology
• Molecular Biology
• Nutritional Science

Background:

• Apical inorganic phosphate (P_i) transport in the small intestine is crucial for phosphate homeostasis.
• The sodium/P_i cotransporter NaPi2b has been implicated as the primary mediator of this transport.

Purpose of the Study:

• To investigate the roles of NaPi2b, PiT1, and PiT2 in intestinal P_i transport.
• To elucidate the combined effects of dietary P_i, pH, and phosphonoformate on P_i transport dynamics.

Main Methods:

• Rats were subjected to varying dietary P_i levels (0.1%, 0.6%, 1.2%) for different durations (1, 5, 10 days).
• Brush-border membrane vesicles were used to assess P_i transport under different pH conditions and in the presence of phosphonoformate.
• Protein abundance of PiT1, PiT2, and NaPi2b was quantified using Western blotting.

Main Results:

• Phosphate deprivation increased both sodium-activated and sodium-independent P_i transport.
• Alkaline pH inhibited P_i transport, while acidic pH increased it, with effects varying based on substrate concentrations.
• Phosphonoformate significantly inhibited basal and upregulated transport, suggesting its role as a P_i transporter inhibitor.
• PiT2 and NaPi2b expression increased rapidly with P_i deprivation, while PiT1 expression showed a delayed response.
• Dietary P_i content and feeding schedules influenced transporter expression inconsistently.

Conclusions:

• Existing transporters (NaPi2b, PiT1, PiT2) do not fully explain the observed intestinal P_i transport under various conditions.
• Findings suggest the presence of a novel sodium-coupled P_i transporter with a preference for [Formula: see text] and sensitivity to phosphonoformate.
• This newly identified transporter's expression correlates with P_i transport across all experimental conditions, highlighting its significance in phosphate absorption.