Effect of Nicotinamide on Phosphate Uptake by Renal Brush Border Membrane Vesicles (BBMV) from Superficial and Juxta-Medullary Cortex in Rats Fed a Normal (NPD) or Low Pi Diet (LPD)

The renal proximal tubule in the kidney is the major site of phosphate (Pi) conservation through controlled reabsorption and excretion. Na-dependent transport of Pi across proximal tubular brush border membrane (BBM) is an essential step that is regulated by hormones, drugs and diet. Phosphaturic hormone; parathyroid hormone and calcitonin have been shown to inhibit Pi transport in nephron segments and BBM populations under different dietary situations differently. In the present study we have investigated the effect of nicotinamide (NiAm), a non-hormone phosphaturic agent on Pi reabsorption in vivo by clearance studies and in BBM vesicles from superficial (SC) and juxta-medullary cortex (JM) in normal (NPD) and low Pi diet (LPD) fed rats. The clearance studies indicate that NiAM caused phosphaturia and decreased Pi reabsorption in vivo in rats fed NPD but had no phosphaturic effect in rats fed LPD.The effect of NiAm onuptake of Pi32 and L-[3H]-Proline was then determined in BBMV-SC and BBMV-JM prepared from same kidneys of the same animals. Administration of NiAm caused phosphaturia and inhibited Pi transport both in BBMV-SC and BBMV-JM to the same degree in rats fed NPD. However, in rats fed LPD, NiAm failed to increase urinary excretion of Pi but inhibited Pitransport in BBMV-SC and not in BBMV-JM. The transport of L-proline, however, was not affected by NiAm in any case. Inhibition of Pi uptake in BBMV-JM rather than that in BBMV-SC seems to be associated with increased urinary excretion of Pi. NiAm also increased NAD content in BBMV-SC and BBMV-JM but to greater extent in NPD compared to LPD rats. NiAm elicited increase of NAD in BBMVs appeared to be the modulator of Pi reabsorption in vivo and in BBMV-SC and BBMV-JM inrats fed NPD and only in BBMV-JM in rats fed LPD.

Keywords: Kidney, Proximal tubule, superficial cortex, juxta-medullary cortex, renal heterogeneity, Na+-dependent Pi transport, nicotinamide, NAD, phosphate deprivation.