BACKGROUND: We recently reported that the administration of niceritorol (a nicotinic acid derivative which improves lipid metabolism and peripheral circulation, and is used for the treatment of hyperlipidaemia and impaired peripheral circulation) to patients with hyperphosphataemia undergoing dialysis decreased the serum phosphate (Pi) concentration. We found that this was due to an acceleration of faecal Pi excretion by niceritrol. METHODS: Intestinal brush border membrane vesicles (BBMVs) were prepared from rat jejunum, and the Na+-dependent and Na+-independent Pi transport activities in these vesicles were measured. In addition, the functional Pi transporter from rat small intestine was injected in Xenopus oocytes, and the effect of nicotinamide on the levels of its expression were measured by northern blotting. RESULTS: The Na+-dependent component was significantly decreased in the BBMVs isolated from rats treated with nicotinamide, while the Na+-independent component was not changed. Kinetic studies demonstrated that the decreased activity was due to reduction of the Vmax value and not an elevation of the Km values. When poly(A)+RNA from rats treated with nicotinamide was microinjected into Xenopus oocytes, the Pi transport activity was significantly decreased compared with that in the control animals. In addition, there were no significant changes in Na/Pi cotransporters and activators, but the vitamin D receptor mRNA level was reduced to 80% of the control level. CONCLUSIONS: These observations suggest that nicotinamide may regulate the expression of a major functional Na/Pi cotransporter in the rat small intestine.
BACKGROUND: We recently reported that the administration of niceritorol (a nicotinic acid derivative which improves lipid metabolism and peripheral circulation, and is used for the treatment of hyperlipidaemia and impaired peripheral circulation) to patients with hyperphosphataemia undergoing dialysis decreased the serum phosphate (Pi) concentration. We found that this was due to an acceleration of faecal Pi excretion by niceritrol. METHODS: Intestinal brush border membrane vesicles (BBMVs) were prepared from rat jejunum, and the Na+-dependent and Na+-independent Pi transport activities in these vesicles were measured. In addition, the functional Pi transporter from rat small intestine was injected in Xenopus oocytes, and the effect of nicotinamide on the levels of its expression were measured by northern blotting. RESULTS: The Na+-dependent component was significantly decreased in the BBMVs isolated from rats treated with nicotinamide, while the Na+-independent component was not changed. Kinetic studies demonstrated that the decreased activity was due to reduction of the Vmax value and not an elevation of the Km values. When poly(A)+RNA from rats treated with nicotinamide was microinjected into Xenopus oocytes, the Pi transport activity was significantly decreased compared with that in the control animals. In addition, there were no significant changes in Na/Pi cotransporters and activators, but the vitamin D receptor mRNA level was reduced to 80% of the control level. CONCLUSIONS: These observations suggest that nicotinamide may regulate the expression of a major functional Na/Pi cotransporter in the rat small intestine.
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