Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine

Background. We recently reported that the administration of niceritorol (a nicotinic acid derivative which improves lipid metabolism and peripheral ci rculation, and is used for the treatment of hyperlipidaemia and impaired pe ripheral circulation) to patients with hyperphosphataemia undergoing dialys is 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 fr om rat jejunum, and the Na+-dependent and Na+-independent Pi transport acti vities in these vesicles were measured. In addition, the functional Pi tran sporter from rat small intestine was injected in Xenopus oocytes, and the e ffect of nicotinamide on the levels of its expression were measured by nort hern blotting. Results. The Na+-dependent component was significantly decreased in the BBM Vs 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 V-max value and not an elevation of th e K-m values. When poly(A)(+)RNA from rats treated with nicotinamide was mi croinjected into Xenopus oocytes, the Pi transport activity was significant ly 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 intes tine.