Effects of reducing and oxidizing agents on the adenylate cyclase activity in adipocyte plasma membranes

Löw, H.; Werner, Sigbritt

doi:10.1016/0014-5793(76)80629-1

Cited by 49 publications

(6 citation statements)

References 14 publications

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“…Halfmaximal inhibition occurs at 20 µM NADH. Other authors have reported that NADH also inhibits adenylate cyclase (26,27). In this case, the concentration for half-maximal inhibition is considerably higher, namely 3 mM (26).…”

Section: Discussionmentioning

confidence: 67%

“…Other authors have reported that NADH also inhibits adenylate cyclase (26,27). In this case, the concentration for half-maximal inhibition is considerably higher, namely 3 mM (26). These observations may appear contradictory, but, as commented by Rashed and Patel (18), whether cAMP accumulates in any given metabolic condition is ultimately determined by the relative inhibition of the cAMP synthesizing and metabolizing enzymes.…”

Section: Discussionmentioning

confidence: 86%

“…At low lactate to pyruvate ratios (low NADH to NAD + ratios), gluconeogenesis is not favored by at least three negative factors: a) reduced cAMP levels due to the higher phosphodiesterase activity relative to the adenylate cyclase activity (18,26), b) reduced Ca 2+ movements so that respiration as well as the activity of several key enzymes cannot be increased (18), and c) insufficiency of reducing power in the cytosol due to inhibition of the phosphoenolpyruvate/pyruvate cycle (28). In Ca 2+ -depleted livers perfused with Ca 2+ -free medium and at low lactate to pyuvate ratios the Ca 2+ movements are probably completely absent.…”

Section: Discussionmentioning

confidence: 99%

“…As the NADH to NAD + ratios are gradually elevated by the increasing lactate to pyruvate ratios in the inflowing perfusate, gluconeogenesis is gradually increased by a number of positive events which are more or less the opposite of those occurring at low NADH to NAD + ratios: a) cAMP accumulates because of the lower phosphodiesterase activity relative to the adenylate cyclase activity (18,26), b) the Ca 2+ movements are increased so that mitochondrial respiration as well as key enzymes can be adequately stimulated (11,13,18,31), and c) the reducing equivalents are now readily available so that an inhibition of pyruvate kinase even favors gluconeogenesis (28). In Ca 2+ -depleted livers perfused with Ca 2+ -free medium, however, gluconeogenesis is limited by the almost complete absence of Ca 2+ .…”

Section: Discussionmentioning

confidence: 99%

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Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

Marques-da-Silva¹,

D'Avila²,

Ferrari³

et al. 1997

Braz J Med Biol Res

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The influence of Ca 2+ on hepatic gluconeogenesis was measured in the isolated perfused rat liver at different cytosolic NAD + -NADH potentials. Lactate and pyruvate were the gluconeogenic substrates and the cytosolic NAD + -NADH potentials were changed by varying the lactate to pyruvate ratios from 0.01 to 100. The following results were obtained: a) gluconeogenesis from lactate plus pyruvate was not affected by Ca 2+ -free perfusion (no Ca 2+ in the perfusion fluid combined with previous depletion of the intracellular pools); gluconeogenesis was also poorly dependent on the lactate to pyruvate ratios in the range of 0.1 to 100; only for a ratio equal to 0.01 was a significantly smaller gluconeogenic activity observed in comparison to the other ratios. b) In the presence of Ca 2+ , the increase in oxygen uptake caused by the infusion of lactate plus pyruvate at a ratio equal to 10 was the most pronounced one; in Ca 2+ -free perfusion the increase in oxygen uptake caused by lactate plus pyruvate infusion tended to be higher for all lactate to pyruvate ratios; the most pronounced difference was observed for a lactate/pyruvate ratio equal to 1. c) In the presence of Ca 2+ the effects of glucagon on gluconeogenesis showed a positive correlation with the lactate to pyruvate ratios; for a ratio equal to 0.01 no stimulation occurred, but in the 0.1 to 100 range stimulation increased progressively, producing a clear parabolic dependence between the effects of glucagon and the lactate to pyruvate ratio. d) In the absence of Ca 2+ the relationship between the changes caused by glucagon in gluconeogenesis and the lactate to pyruvate ratio was substantially changed; the dependence curve was no longer parabolic but sigmoidal in shape with a plateau beginning at a lactate/pyruvate ratio equal to 1; there was inhibition at the lactate to pyruvate ratios of 0.01 and 0.1 and a constant stimulation starting with a ratio equal to 1; for the lactate to pyruvate ratios of 10 and 100, stimulation caused by glucagon was much smaller than that found when Ca 2+ was present. e) The effects of glucagon on oxygen uptake in the presence of Ca 2+ showed a parabolic relationship with the lactate to pyruvate ratios which was closely similar to that found in the case of gluconeogenesis; Key wordsBraz J Med Biol Res 30 (7) 1997 A.C. Marques-da-Silva et al.the only difference was that inhibition rather than stimulation of oxygen uptake was observed for a lactate to pyruvate ratio equal to 0.01; progressive stimulation was observed in the 0.1 to 100 range. f) In the absence of Ca 2+ the effects of glucagon on oxygen uptake were different; the dependence curve was sigmoidal at the onset, with a welldefined maximum at a lactate to pyruvate ratio equal to 1; this maximum was followed by a steady decline at higher ratios; at the ratios of 0.01 and 0.1 inhibition took place; oxygen uptake stimulation caused by glucagon was generally lower in the absence of Ca 2+ except when the lactate to pyruvate ratio was equal to 1. The results of the prese...

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

Marques-da-Silva¹,

D'Avila²,

Ferrari³

et al. 1997

Braz J Med Biol Res

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“…NADH dehydrogenase acts as a sensor for the redox state of the cell which controls the response of adenylyl cyclase to hormones [2,3].…”

Section: Introductionmentioning

confidence: 99%

Activation of a NADH Dehydrogenase in the Human Erythrocyte by Beta-Adrenergic Agonists: Possible Involvement of a G Protein in Enzyme Activation

Marques

Bicho

1997

Neurosignals

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NADH dehydrogenase in the plasma membrane transfers electrons from NADH to external oxidants like ferricyanide, through pathways which are linked to metabolic processes in the cell. Hormone binding to specific sites (receptors) can modify the enzyme activity, suggesting a direct or indirect coupling between the redox system and the hormone receptors. Reduction of external ferricyanide to ferrocyanide by human erythrocytes was stimulated by β-adrenergic agonists (adrenaline, ritodrine and isoxsuprine), this effect being dependent upon concentration and pH. The agonist-stimulatory effect was attenuated in the presence of metoprolol (10^–4M), a β-adrenergic antagonist, and was not modified in the presence of prazosin, an α-adrenergic antagonist, suggesting that modification of the redox activity is mediated by binding of the agonists to β-adrenergic receptors present in the human erythrocytes. Basal and agonist-dependent activities were inhibited in the presence of sulfhydryl reagents p-chloromercuriben-zoate (PCMB, 10^–5M) and N-ethylmaleimide (NEM, 10^–3M), indicating the involvement of –SH groups. Inactivation by NEM was reversed by washing the cells with GTP (10^–3M) and GTPγS (10^–4M), suggesting that the specific alkylated –SH group(s) is located on a G protein in the hormone-receptor-G-protein complex. The human erythrocytes contain G proteins, displaying both guanine-nucleotide-binding properties and GTPase activity. Fluoride (10^–2 M) and fluoroaluminate AlF^–₄ (F^–, 10^–2M + Al³⁺, 10^–5M), G protein activators, enhanced the basal and agonist-dependent activities, suggesting the involvement of G proteins in this system. The overall results indicated that one of the coupling components between the hormonal receptors and the redox system is probably a G protein, and the mechanism of enzyme activation after hormone binding to the receptor is based on the redox state of cysteine residues probably within the receptor-G-protein complex.

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Amino acid transport systems in animal cells: Interrelations and energization

Christensen

1977

J Supramol Struct

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After summarizing the discrimination of the several transport systems for neutral amino acids in the cell of the higher animal, I discuss here the ways in which 2 dissimilar transport systems interact, so that one tends t o run torward for net entry and the other backwards for net exodus. An evaluation of the proposals for energization shows that uphill transport continues when neither alkali-ion gradients nor ATP levels are favorable. Evidence is presented that under these conditions a major contribution is made by another mode of energization, which may depend on the fueling of an oxidoreductase in the plasma membrane. This fueling may involve the export by the mitochondrion of the reducing equivalents of NADH by one of the known shuttles, e.g., the malate-aspartate shuttle. After depletion of the energy reserves in the Ehrlich cell by treating it with dinitrophenol plus iodoacetate concentrative uptake of test amino acids is restored by pyruvate, but in poor correlation with the restoration of alkali-ion gradients and ATP levels. This restoration by pyruvate but not by glucose is highly sensitive to rotenone. A combination of phenazine methosulfate and ascorbate will also produce transport restoration, before either the alkali-ion gradients or ATP levels have begun to rise. The restoration of transport applies to a model amino acid entering by the Na+-independent system, as well as to one entering by the principal Na+-dependent system, restoration being blocked by ouabain, despite the weak effect of ouabain on the alkali-ion gradients in the Ehrlich cell. Quinacrine terminates very quickly the uptake of model amino acids, before the alkali-ion gradients have begun to fall and before the ATP level has been halved. Quinacrine is also effective in blocking restoration of uphill transport by either pyruvate or the phenazine reagent. Preliminary results show that vesicles prepared from the plasma membrane of the Ehrlich cell quickly reduce cytochrome c or ferricyanide in the presence of NADH, and that the distribution of a test amino acid between the vesicle and its environment is influenced by NADH, quinacrine, and an uncoupling agent in ways consistent with the above proposal, assuming that a majority of the vesicles are everted.Key words: amino acid transport in animal cells, energization of transport systems, discrimination of transport systems, reverse operation of transport systems, Ehrlich cell, NADH dehydrogenase, alkali-ion gradients, phenazine methosulfate, ouabain TRANSPORT SYSTEMS AND THEIR INTERACTIONThe transport systems for neutral amino acids in the Ehrlich cell are taken t o be approximately representative of those of the cells of the higher animal in general, with more and more evidence supporting that interpretation. Most conspicuous are a broad-

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Effects of reducing and oxidizing agents on the adenylate cyclase activity in adipocyte plasma membranes

Cited by 49 publications

References 14 publications

Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

Ca2+ dependence of gluconeogenesis stimulation by glucagon at different cytosolic NAD+-NADH redox potentials

Activation of a NADH Dehydrogenase in the Human Erythrocyte by Beta-Adrenergic Agonists: Possible Involvement of a G Protein in Enzyme Activation

Amino acid transport systems in animal cells: Interrelations and energization

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