Barbiturates and oxidative phosphorylation

Aldridge, W. N.; Parker, V. H.

doi:10.1042/bj0760047

Cited by 110 publications

(28 citation statements)

References 37 publications

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“…One plausible explanation for the failure of bar biturates to protect cortical neurons against damage by oxygen or glucose deprivation might be that these compounds exacerbate the cellular energy de pletion induced by these insults. Barbiturates are known to inhibit oxidative phosphorylation (Brody and Bain, 1954;Aldridge and Parker, 1960;Chance and Hollunger, 1963) and thus might promote more rapid depletion of cellular ATP stores.…”

Section: Resultsmentioning

confidence: 99%

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Giffard

Weiss

Swanson

et al. 1993

J Cereb Blood Flow Metab

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Summary:We examined the effects of secobarbital and other sedative-hypnotic barbiturates on the neuronal death induced by exposure to excitatory amino acids or deprivation of oxygen or glucose in mouse cortical cell cultures. N-Methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, and kainate toxicities were attenuated in a concentration-dependent fashion by high concentrations of secobarbital or thiopen tal. Antagonism of NMDA toxicity was not overcome by increasing NMDA concentration and not mimicked by ,),-aminobutyrate. Despite these antiexcitotoxic actions, secobarbital exacerbated the neuronal death induced byBarbiturates are used clinically as sedatives, an esthetics, and anticonvulsants and have long been of interest as a method for reducing hypoxic ischemic brain injury. Twenty-five year ago, these drugs were found to prolong the survival of mice breathing 5% oxygen better than several other an esthetic agents (Wilhjelm and Arnfred, 1965). Sub sequently, high doses of barbiturates have been demonstrated to provide brain protection in several

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Section: Resultsmentioning

confidence: 99%

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Giffard

Weiss

Swanson

et al. 1993

J Cereb Blood Flow Metab

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“…Simultaneous measurements of 02 consumption and tension change of the muscle strips Amytal is one of the electron transport inhibitors in the NADH-cytochrome b segment of the mitochondrial respiratory chain (12). Refer to the note in Fig.…”

Section: Resultsmentioning

confidence: 99%

The Regulation of Respiration of Guinea Pig Taenia Coli in High-K Medium; The Role of Nicotinamide-Adenine Dinucleotide, Adenosine Diphosphate and Ca++

Tsuda

Urakawa

Saitō

et al. 1975

Japanese Journal of Pharmacology

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Abstract-In an attempt to elucidate the regulation mechanism of respiration in the smooth muscle cell, we investigated the roles of nicotinamide-adenine dinucleotide (NAD), adenosine diphosphate (ADP) and Ca" in the muscle respiration using the tissues and subcellular fractions from guinea pig taenia coli. The tension in the strips of taenia coli increased with a concomitant increase in 02 consumption in high-K medium (40 mM K) containing 2.5 mM Ca. 10-3 M amytal and 10-6 M ouabain decreased the high-K induced tension and 02 consumption of the muscle. 10-4 M 2,4-dinitrophenol (DNP) relieved the decreased respiration induced by ouabain, but not that with amytal. From these data it is suggested that NADH-linked respiration plays an important role in the respiration of the muscle. Ca++ in concentrations ranging from 0.5 to 2.5 mM in the high-K medium resulted in an increase in tension and in 02 consumption progressively. In spectrophotometric observations of subcellular fractions of the taenia coli, ADP increased in absorbance change at 340 mtg. Such occurred in mitochondrial fractions and was initiated by the addition of NADH. Therefore it is deduced that the increase in ADP level of the cytoplasm is primarily due to a contraction triggered by Ca" thus stimulating respiration. On the other hand, at 0.1 mM of Ca++ concentration, the muscle strip increased O2 consumption without tension development in high-K medium. In the spectrophotometric obser vations, Ca++ and Sr++ increased the absorbance change in the homogenate and in the mitochondrial fraction. Hence, it seems that one part of the Ca++ entering into the smooth muscle treated with the high-K increased O2 consumption in mitochondria independent of an increase in muscle tension. From these results it is concluded that NADH-linked respiration plays an important role in the smooth muscle respi ration in high-K medium and that ADP and Ca++ also play a role in regulating res piration.It has been reported that the smooth muscle of guinea pig taenia coli requires the aerobic breakdown of carbohydrate to maintain a continuous tension in a high-K (40 mM) medium(1) and that during the tonic contraction, Ca++ enters across the cell membrane into the muscle (2) and also that both the changes in tension and Ca++ movement induced by the high-K are abolished by an application of 10-4M DNP or anoxia (3). In preliminary work we have found that the inhibitors of NADH oxidation in mitochondrial respiratory

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“…First, in the presence of 30 aM-2,4-dinitrophenol the rate of hydrolysis was not linear and rapidly decreased after 3,uzmol of the 9,umol of ATP had been hydrolysed. The initial rate was 530nmol of Pi/min per mg of protein compared with 220nmol of Pi/min per mg of protein when the average rate over lOmin was determined (Aldridge & Stoner, 1960 & Parker, 1960;Aldridge & Stoner, 1960). When rotenone (lnmol/mg of protein) was added a higher rate was obtained (Table 2).…”

mentioning

confidence: 99%

Oxidative phosphorylation. The relation between the specific binding of trimethlytin and triethyltin to mitochondria and their effects on various mitochondrial functions

Aldridge

Street

1971

Biochemical Journal

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1. A binding site (site 1) is present in mitochondria with affinity for trimethyltin and triethyltin adequate for a site to which they could be attached when the processes of energy conservation are inhibited. 2. The quantitative relationships between the binding of trimethyltin and triethyltin to site 1 and their effects on various mitochondrial functions have been examined. 3. ATP synthesis linked to the oxidation of pyruvate, succinate and intramitochondrial substrate, ATP synthesis and oxygen uptake (succinate or pyruvate as substrate) stimulated by uncoupling agents are all inhibited by trimethyltin and triethyltin; when inhibition is less than 50% the ratio (percentage inhibition)/(percentage of binding site 1 complexed) is approx. 10:1. 4. ATP synthesis linked to the oxidation of reduced cytochrome c (ascorbate+NNN′N′-tetramethyl-p-phenylenediamine), ATP hydrolysis and oxygen uptake in the presence of low concentrations of trimethyltin and triethyltin approach zero activity as the proportion of binding site 1 complexed approaches 100%. 5. Possible interpretations of these findings are discussed with reference to published arrangements for coupling of electron transport to ATP synthesis and also to our present knowledge of the chemical and biological specificity of trialkyltin compounds.

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Barbiturates and oxidative phosphorylation

Cited by 110 publications

References 37 publications

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

The Regulation of Respiration of Guinea Pig Taenia Coli in High-K Medium; The Role of Nicotinamide-Adenine Dinucleotide, Adenosine Diphosphate and Ca++

Oxidative phosphorylation. The relation between the specific binding of trimethlytin and triethyltin to mitochondria and their effects on various mitochondrial functions

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