DEVELOPMENTAL-CHANGES IN PURINE NUCLEOTIDE-METABOLISM IN CULTURED RATASTROGLIA

The present study was conducted in order to clarify the role of the gl ia in brain purine metabolism. This, in connection with the clarificat ion of the etiology of the neurological manifestations associated with some of the inborn errors of purine metabolism in man. Purine nucleot ide content, the capacity for de novo and salvage purine synthesis and the activity of several enzymes of purine nucleotide degradation, wer e assayed in primary cultures of rat astroglia in relation to culture age. The capacity of the intact cells to produce purine nucleotides de novo exhibited a marked decrease with the culture age, but the activi ty of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), catalyzi ng salvage nucleotide synthesis, increased. Aging was also associated with a marked increase in the activity of the degradation enzymes AMP deaminase, purine nucleoside phosphorylase (PNP) and guanine deaminase (guanase). The activity of adenosine deaminase and of AMP-5'-nucleoti dase, increased markedly during the first 17 days in culture,but decre ased thereafter. The results indicate that purine nucleotide metabolis m in the cultured astroglia is changing with aging to allow the cells to maintain their nucleotide pool by reutilization of preformed hypoxa nthine, rather than by de-novo production of new purines. Aging is als o associated with increased capacity for operation of the adenine nucl eotide cycle, contributing to the homeostasis of adenine nucleotides a nd to the energy charge of the cells. In principle, the age-related al terations in purine metabolism in the astroglia resemble those occurri ng in the maturating neurons, except for the capacity to produce purin es denovo, which exhibited inverse trends in the two tissues. However, in comparison to the neurons, the cultured astroglia possess the capa city for a more intensive metabolism of purine nucleotides.