Molecular Pharmacology, Vol 10, 381-388, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Comparison of Effects of Glucagon and Valinomycin on Rat Liver Mitochondria and Cells

¹ Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22903

It has been shown previously that treatment of rats with glucagon, epinephrine, or cortisol alters the mitochondria of the liver so that the isolated organelles utilize pyruvate at an accelerated rate as measured by disappearance, decarboxylation, or carboxylation of pyruvate. It is reported here that valinomycin added at approximately 10 nM to isolated mitochondria partially mimicked these hormone treatments by stimulating carboxylation and decarboxylation of pyruvate. Valinomycin added in concentrations several times greater than those required for stimulation inhibited carboxylation, apparent1y by depleting mitochondrial ATP, but these same high levels continued to stimulate decarboxylation. The stimulations by this antibiotic were not duplicated by dinitrophenol, suggesting that they depend on the ability of valinomycin to act as an ionophore rather than as an uncoupler. Although similar, the mitochondrial stimulations resulting from treatment with glucagon and addition of valinomycin were additive, suggesting nonidentity of their mechanisms. In another action that resembled that of glucagon, valinomycin (10 nM) stimulated glucose synthesis from lactate in isolated liver cells. This effect of valinomycin was shown not to be mediated through the agency of adenosine cyclic 3',5'-monophosphate.

Note:
ACKNOWLEDGMENT The technical assistance of Kathy Borland and Adele Marshall is gratefully acknowledged.

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