Actinomycin D Inhibition of the Adaptation of Renal Glutamine-deaminating Enzyme in the Rat

Abstract

PREVIOUS investigations have shown that metabolic acidosis leads to significant increases in the activities of glutaminase and glutamine transaminase-ω-amidase (GTA) in kidneys of rats^1,2 and guinea-pigs³. These changes are associated with, and thought to be related to, the adaptation of renal ammonia excretion to acidosis in the rat^2,4 and guinea-pig³. The response of renal glutaminase to metabolic acidosis is not mediated by the adrenal gland⁵ or substrate, glutamine⁶, and is restricted to the kidneys⁵. Goldstein and Kensler⁵ found that administration of ethionine to guinea-pigs inhibited the acid-induced rise in renal glutaminase activity, and we suggested that metabolic acidosis stimulates the synthesis of glutaminase by renal cells. The manner in which this stimulation occurs is unknown. Kroeger⁷ has recently reported that alterations in the electrolyte balance of the medium bathing isolated salivary glands of the insect Chironomus thummi produced marked and specific changes in the gene activities (RNA synthesis) of the giant chromosomes found in these glands. Metabolic acidosis and the accompanying changes in electrolyte balance might have similar effects on UNA synthesis in renal cells. Actinomycin D, an antibiotic which interferes with the DNA-dependent synthesis of RNA in bacterial and animal cells⁸, has been shown to inhibit the synthesis of RNA in rat kidneys⁹. The effects of this antibiotic on the responses of renal glutaminase, GTA and ammonia excretion to metabolic acidosis were therefore investigated in the rat.