Control of energy metabolism by glucagon and adrenaline in perfused rat liver

Soboll, Sibylle; Scholz, Roland

doi:10.1016/0014-5793(86)80875-4

Cited by 30 publications

(19 citation statements)

References 18 publications

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“…The PMF is composed of membrane potential (ΔΨ m ) and pH gradient (ΔpH m ) components. Although it has not been shown for vasopressin, a number of previous studies have suggested that gluconeogenic hormones such as glucagon, α‐adrenergic agonists and L ‐triiodothyronine increase the PMF in hepatocyte suspensions and perfused liver (Prpic et al ., 1978; Taylor et al ., 1980; Soboll and Scholz, 1986; Halestrap, 1989; Soboll et al ., 1992; Soboll, 1993). However, the measurements of PMF in these studies were carried out in mitochondrial fractions isolated from the cells or tissue subsequent to hormone treatment.…”

Section: Resultsmentioning

confidence: 99%

Integrating cytosolic calcium signals into mitochondrial metabolic responses

Gaspers¹,

et al. 1998

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Stimulation of hepatocytes with vasopressin evokes increases in cytosolic free Ca2+ ([Ca2+]c) that are relayed into the mitochondria, where the resulting mitochondrial Ca2+ ([Ca2+]m) increase regulates intramitochondrial Ca2+-sensitive targets. To understand how mitochondria integrate the [Ca2+]c signals into a final metabolic response, we stimulated hepatocytes with high vasopressin doses that generate a sustained increase in [Ca2+]c. This elicited a synchronous, single spike of [Ca2+]m and consequent NAD(P)H formation, which could be related to changes in the activity state of pyruvate dehydrogenase (PDH) measured in parallel. The vasopressin-induced [Ca2+]m spike evoked a transient increase in NAD(P)H that persisted longer than the [Ca2+]m increase. In contrast, PDH activity increased biphasically, with an initial rapid phase accompanying the rise in [Ca2+]m, followed by a sustained secondary activation phase associated with a decline in cellular ATP. The decline of NAD(P)H in the face of elevated PDH activity occurred as a result of respiratory chain activation, which was also manifest in a calcium-dependent increase in the membrane potential and pH gradient components of the proton motive force (PMF). This is the first direct demonstration that Ca2+-mobilizing hormones increase the PMF in intact cells. Thus, Ca2+ plays an important role in signal transduction from cytosol to mitochondria, with a single [Ca2+]m spike evoking a complex series of changes to activate mitochondrial oxidative metabolism.

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Section: Resultsmentioning

confidence: 99%

Integrating cytosolic calcium signals into mitochondrial metabolic responses

Gaspers¹,

et al. 1998

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“…There is, on the other hand, a report showing that the concentration of ornithine in isolated hepatocytes is 1.6 mM in the mitochondrial matrix and 0.6 mM in the cytosol [26]. If these measurements are correct, since the ∆pH across the mitochondrial membrane in perfused liver is about 0.33 unit [27], a concentration gradient of citrulline (in\out) of 5.3 should be sufficient to drive entry of ornithine in exchange for intramitochondrial citrulline. A comparable citrulline gradient is not unlikely to exist in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

The purified and reconstituted ornithine/citrulline carrier from rat liver mitochondria: electrical nature and coupling of the exchange reaction with H+ translocation

Indiveri

Tonazzi

Stipani

et al. 1997

Biochemical Journal

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The mechanism and the electrical nature of ornithine/citrulline exchange has been investigated in proteoliposomes reconstituted with the ornithine/citrulline carrier purified from rat liver mitochondria. The stoichiometry of the exchanging substrates was close to 1:1. The exchange was not affected by inducing electrogenic flux of K+ with valinomycin. In contrast, the pH gradient generated by the K+/H+ exchanger nigericin in the presence of an outwardly directed K+ gradient stimulated the ornithineout/citrullinein exchange, but not the ornithine/ornithine homoexchange. Experiments in which either the internal or the external pH was varied, while keeping constant the pH in the other compartment, indicated that maximal exchange rates are found at pH 6 in the compartment containing citrulline and at pH 8 in the compartment containing ornithine. Changes in fluorescence of the pH indicator pyranine, included inside the proteoliposomes, showed that the exchanges ornithineout/citrullinein and citrullineout/ornithinein are accompanied by translocation of H+ in the same direction as citrulline. It is concluded that the mitochondrial ornithine/citrulline carrier catalyses an electroneutral exchange of ornithine+ for citrulline plus an H+. A reasonable model is one in which ornithine binds to a deprotonated carrier and citrulline to a protonated carrier and both substrate-carrier complexes are neutral. The physiological implications of this transport process are discussed.

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“…The physiological significance of APC isoforms is highlighted by the observation that changes in the adenine nucleotide concentration in the mitochondrial matrix, without variation in the whole cell content, occur in many adaptive states. For example, the mitochondrial adenine nucleotide pool has been found to be increased in newborn liver mitochondria 3-4 times within 3-4 h after birth (35) and in adult liver mitochondria upon fasting (50,51), after glucagon treatment (50 -52), and in altered thyroid states (53). On the other hand, it is decreased by hypoxia (54) and ischemia (55), in fast growing hepatomas (56), during hibernation (57), and in copper deficiency (58).…”

Section: Influence Of Membrane Potential and Ph Gradient On The Apc-mmentioning

confidence: 99%