Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat

S. A. Kempson, G. Colon-Otero, S. Y. Ou, S. T. Turner, T. P. Dousa

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

In these experiments we investigated whether NAD could serve as an intracellular modulator of the brush border membrane (BBM) transport of inorganic phosphate (Pi). NAD, both oxidized (NAD+) and reduced (NADH) form, inhibited the Na+dependent uptake of 32Pi in the concentration range of 10-300 μM NAD when added in vitro to BBM vesicles isolated from rat kidney cortex, but did not inhibit BBM uptake of D-[3H]glucose or BBM uptake of 22Na+. Neither nicotinamide (NiAm) nor adenosine alone influenced BBM uptake of 32Pi. NAD had a similar relative effect (percent inhibition) in BBM from rats stabilized on low Pi diet (0.07% Pi), high Pi diet (1.2% Pi), or normal Pi diet (0.7% Pi). Subsequently, we examined the renal effects of changing the tissue NAD level in vivo. Rats stabilized on low Pi diet were injected intraperitoneally with NiAm (0.25-1.0 g/kg body wt); urinary excretions of Pi (U(Pi)V), or fluid, and of other solutes were measured before and after NiAm injection, then renal cortical tissue nucleotide content was determined, and a BBM fraction was isolated for transport measurements. In BBM from NiAm-treated rats, the Na+-dependent uptake of 32Pi was decreased, but BBM uptake of D-[:3H]glucose and BBM uptake of 22Na were not changed. NiAm injection elicited an increase in NAD+ (maximum change, 290%), a lesser increase in NADH (maximum change, +45%), but no change in the content of ATP or cyclic AMP in the renal cortex. Na+-dependent BBM uptake of 32Pi was inversely correlated with NAD+ content in renal cortex (r = -0.77 ± 0.1; P < 0.001) and with U(Pi)V (r = 0.67 ± 0.13; P < 0.01). NAD+ in renal cortex was positively correlated with U(Pi)V (r= 0.88 ± 0.05; P < 0.001). Injection of NiAm elicited a marked increase in U(Pi)V, but no change in excretions of creatinine or K+, or in urine flow; excretion of Na+ and Ca declined. NiAm injection caused similar renal responses, in normal and in thyroparathyroidectomized rats, as well as in rats on normal Pi diet and low Pi diet. We conclude that NAD can serve as an intracellular modulator (inhibitor) of Na+-dependent transport of Pi across the renal luminal BBM and across the proximal tubular wall by its direct interaction with BBM. We propose that at least some hormonal and/or metabolic stimuli elicit phosphaturia by increasing NAD+ in cytoplasm of proximal tubular cells.

Original languageEnglish (US)
Pages (from-to)1347-1360
Number of pages14
JournalUnknown Journal
Volume67
Issue number5
DOIs
StatePublished - 1981

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat'. Together they form a unique fingerprint.

  • Cite this