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Am J Physiol Regul Integr Comp Physiol 261: R1522-R1526, 1991;
0363-6119/91 $5.00
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AJP - Regulatory, Integrative and Comparative Physiology, Vol 261, Issue 6 1522-R1526, Copyright © 1991 by American Physiological Society

ARTICLES

Inhibition of gluconeogenesis by extracellular ATP in isolated rat hepatocytes

M. Asensi, A. Lopez-Rodas, J. Sastre, J. Vina and J. M. Estrela
Departamento de Fisiologia, Universitat de Valencia, Spain.

The aim of this study was to determine the effect of externally added ATP on gluconeogenesis by isolated hepatocytes from starved rats. High concentrations of extracellular ATP inhibited gluconeogenesis from lactate and pyruvate but not from glycerol or fructose. This inhibition was associated with an increase in intracellular adenosine contents. ADP, AMP, or adenosine but not guanosine 5'triphosphate, inosine 5' triphosphate, or adenine also inhibited gluconeogenesis. alpha, beta-Methylene-ATP, a nonmetabolizable structural analogue of ATP, did not affect the rate of gluconeogenesis. Intracellular ATP levels were increased by externally added ATP or adenosine, but ATP-to-ADP ratios in the cytosolic and mitochondrial compartments were diminished. Malate and phosphoenolpyruvate contents were decreased by extracellular ATP or adenosine. Our results show that inhibition of gluconeogenesis by high levels of extracellular ATP may be mediated by adenosine derived from ATP catabolism at the plasma membrane.


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