Phosphoribosylpyrophosphate bioavailability in diabetic rat renal cortex in vivo

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.