Stimulation of renal gluconeogenesis by exogenous adenine nucleotides

1. Tubule fragments were isolated from renal cortex of fed rats. 2. Gluconeogenesis from lactate was significantly increased by low concentrations of exogenous ATP, ADP, AMP adenylyl (beta, gamma-methylene)diphosphonate and, to a lesser extent, by ITP and inosine. GTP was slightly inhibitory. Hypoxanthine was ineffective. Exogenous adenosine deaminase slightly decreased gluconeogenesis and was additive in effect to GTP. Adenosine deaminase did not abolish the stimulatory effects of ATP or cyclic AMP. 3. 40 microM ATP also stimulated gluconeogenesis from pyruvate, malate, succinate, 2-oxoglutarate and glutamine, but had no effect when glycerol or fructose were used as substrates. 4. With lactate as substrate the effect of 40 microM ATP was additive to the maximal stimulations of gluconeogenesis seen with 1 microM noradrenalin or 0.1 microM angiotensin II, but was not additive to the stimulatory effect of 0.1 mM cyclic AMP. 5.40 microM ATP had no effect upon either the tubule content of cyclic AMP or upon 45Ca efflux from prelabelled tubules. 6. Addition of ouabain or removal of extracellular K+ diminished the stimulatory effects of ATP and cyclic AMP. 7. Extracellular ATP was rapidly metabolized by tubule fragments, with resulting accumulation of adenosine. Further metabolism resulting in formation of inosine, hypoxanthine, xanthine and uric acid was also observed. Cyclic AMP was metabolized less rapidly, with no accumulation of adenosine. 8. The effects of purinergic agents on gluconeogenesis are discussed.