On the inter-relationship between glucagon action, the oxidation-reduction state of pyridine nucleotides, and calcium retention by rat liver mitochondria.

that the oxidation-reduction state of mitochondrial pyridine nucleotides is a determinant in the ability of mitochondria to retain ca'+.Use was made of the fact that glucagon administration to rats in vivo induces a stable enhancement in the ability of the mitochondria subsequently isolated from the liver to retain accumulated CaZ+ (Prpic, V., Spencer, T. L., and Bygrave, F. L.(1978) Biochen J. 176,705-714).Addition of oxalacetate to saline-challenged (control) mitochondria that already had accumulated Ca'+, led within 15 s to the complete oxidation of the mitochondrial NADH.In the same time period, only about 20% of the NADPH had become oxidized and Ca2+ was still retained by the mitochondria.Approximately 30 s after the addition of oxalacetate, the rate of NADPH oxidation slowed about 10-fold at which time the release of Ca'+ from the mitochondria began to occur.The rate of NADH oxidation was similar in mitochondria isolated from glucagon-challenged and from saline-challenged rat liver.That of NADPH oxidation was slower in the glucagon-challenged mitochondria especially during the above-mentioned latter phase.Under identical experimental conditions, Ca'+ was retained by the mitochondria from glucagon-challenged liver but not by those from saline-challenged liver.Other experiments involving variations to either the pH of the incubation medium, or the dose of glucagon administered, provided further evidence of a correlation between the ability of mitochondria to retain Ca2+ and their resistance to oxidize NADPH.A correlation could not be detected between the ability of mitochondria to retain Ca'+ and their ability to oxidize NADH.The data do not permit conclusions t s be drawn about the nature of the mechanisms linking the oxidationreduction state of NADP+-NADPH with that of Ca'+ retention, but an argument is put that the energylinked transhydrogenase reaction that leads to the generation of NADPH and which is stimulated in mitochondria from glucagon-challenged liver, may be involved.