AJP - Endocrinology and Metabolism, Vol 238, Issue 4 341-E348, Copyright © 1980 by American Physiological Society
Phosphoribosylpyrophosphate bioavailability in diabetic rat renal cortex in vivo
P. Cortes, C. P. Verghese, K. K. Venkatachalam, A. M. Schoenberger and N. W. Levin
Experimental diabetes induces increased content of RNA and UTP in the renal
cortex. Studies were designed to assess the bioavailability of
5-phosphoribosyl-1-pyrophosphate (PRPP) in the diabetic renal cortex
because PRPP is an important determinant of the de novo synthesis of
nucleotides. The tissue bioavailability of PRPP determines the effects of
orotate or adenine administration on UTP, ATP, and GTP content and on the
incorporation of labeled precursors into UTP and ATP. Diabetic and control
rats with chronic intravenous cannulas were infused over 2.5-24 h with
orotate or adenine. Orotate administration induced greater decreases in ATP
and GTP and in labeled adenine incorporation into ATP concomitant with
smaller increases in UTP in controls than in diabetic animals. Adenine
administration induced a greater decrease of labeled orotate incorporation
into UTP and a smaller increase in ATP in controls than in diabetic
animals. Prolonging the adenine infusion resulted in disappearance of these
differences. The results are compatible with greater initial
bioavailability of PRPP in the diabetic renal cortex than in controls but
with a rate of maximal PRPP generation that is the same in both tissues.
