Renal handling of polyamines

Ray, Soma (1993) Renal handling of polyamines. Masters thesis, Memorial University of Newfoundland.

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Abstract

Polyamines are aliphatic, organic cations distributed in all living cells. They play an important role in cell proliferation, cell growth and synthesis and metabolism of macromolecules like nucleic acids and proteins. The three principal polyamines in mammalian cells are putrescine, spermidine and spermine. -- Polyamine excretion has been found to be increased in the urine of patients with various types of malignancies. Many workers have advocated the use of urinary polyamines as markers of malignancy and also for monitoring the effectiveness of cancer therapy. To use urinary polyamines for such a purpose it is important to understand how the kidney handles these substances, and to find out what is the source of the urinary polyamines. The present experiments were done to study these aspects of renal polyamine handling. -- In both male and female rats, putrescine was the major polyamine excreted, followed by spermidine and smaller amounts of spermine and the acetylated polyamines. No cadaverine was detected in the urine of any of these rats on a polyamine-free diet. Equilibrium dialysis studies in vitro showed that about 8% of putrescine and 16% of spermidine are non-covalently bound to plasma proteins, therefore, most of the putrescine and spermidine should be filterable. When the excreted load of spermidine was compared to the probable filtered load, using the free spermidine concentration, it was found that only 0.6-1.5% of the spermidine was excreted. The negligible arteriovenous difference in whole blood and plasma indicates that almost all of the spermidine entering the glomerulus is returned to the renal circulation. Thus reabsorption is the predominant fate of the spermidine filtered at the glomerular membrane. On the other hand, a higher proportion of the filtered putrescine was excreted, although this still only ranged from 14% (female) to 29% (male) of the probable filtered load in untreated rats. Much more putrescine is removed from the red blood cells as they pass through the kidney than what is excreted. The metabolic fate of this putrescine is not known. -- In order to test whether reabsorption occurred in the proximal tubule, female rats were treated with maleate to produce an experimental Fanconi syndrome characterized by a generalized disruption of the reabsorption processes in the proximal renal tubule. Polyamine excretion was compared with that from saline-treated control rats. Maleate treatment for four hours produced polyuria, glucosuria and aminoaciduria. There was a significant drop in the plasma spermidine level and a significant decrease in the filtered load of spermidine. The plasma putrescine delivery and the plasma level remained unaltered due to maleate treatment. There was a significant decrease in the percentage reabsorption of both putrescine and spermidine. It was concluded that maleate interferes with polyamine reabsorption as it does with reabsorption of amino acids and other substances by the proximal tubule. Spermidine reabsorption by the kidney may play an important role in maintaining its plasma level; an interference of reabsorption producing excess excretion causes a failure to maintain plasma spermidine levels. On the other hand, plasma putrescine level may have a tighter regulation, which prevents a decrease in plasma concentration even when its excretion is increased due to interference in reabsorption.

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