Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

The opioid agonists morphine (selective for mu-receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Failure of opioids to affect excitation and contraction in isolated ventricular heart muscle

Summary The opioid agonists morphine (selective for -receptors) and ethylketocyclazocine (selective for kappa-receptors), at concentrations evoking strong effects in neuronal structures, did not significantly affect the configuration of the intracellularly recorded action potential and the force of contraction in ventricular heart muscle isolated from guinea pigs, rabbits and man. These results suggest that any changes of heart functions in vivo in response to opioid-like drugs are probably not mediated postsynaptically at the myocardial cell membrane but rather presynaptically, influencing the release of noradrenaline and/or acetylcholine from the nerve terminals.     

Effect of acute and exhaustive exercise upon the fine structure of heart mitochondria

Zusammenfassung Eine deutliche Vermehrung der Mitochondrienzahl und -grösse in den Herzrmiskelzellen wurde in Hunden durch erzwungenes Schwimmen (rasche und erschöpfende Leistung) festgestellt.     

Deoxyribonucleic acid synthesis in the heart mitochondria after acute and exhaustive exercise

Resumen Las mitocondrias del corazón de ratas sometidas a natación forzada muestran filamentos considerados morfológicamente como de ADN y captan timidina tritiada. Sobre la base de estas observaciones se sugiere que las mitocondrias miocárdicas con capaces de una activa síntesis de ADN como respuesta a requirimientos funcionales agudos.     

The inhibitory effect of sodium on the contraction of frog's heart perfused with sucrose solution

Résumé Le cur de grenouille continue à battre de lui-même et répond à une stimulation électrique durant 5–6 h s'il reçoit une injection contenant une demi solution isotonique de saccharose, de pyrophosphate de sodium et d'adénosinetriphosphate ou de citrate de sodium. Le chloride de sodium annule ces deux réactions.     

Metabolic status of temperature induced swollen conidia ofAspergillus nidulans

Summary There is an active synthesis of DNA, RNA, protein, and carbohydrate in conidia incubated at 48°C. DNA increases more or less 3 times; while RNA, protein and carbohydrate are synthesized at a much faster rate. Conidia do not germinate at this temperature.Acknowledgments. Grateful thanks are due to Professor B. M. Johri for valuable suggestions. R. K. S. acknowledges with thanks a Senior Research Fellowship of the Council of Scientific and Industrial Research, New Delhi.     

Role of nitric oxide in the functional response to ischemia-reperfusion of heart mitochondria from hyperthyroid rats

We investigated the role of nitric oxide (NO) in the mitochondrial derangement associated with the functional response to ischemia-reperfusion of hyperthyroid rat hearts. Mitochondria were isolated at 3000 g from hearts subjected to ischemia-reperfusion, with or without N-nitro-L-arginine (L-NNA, an NO synthase inhibitor). During reperfusion, hyperthyroid hearts displayed tachycardia and low functional recovery. Their mitochondria exhibited O₂ consumption similar to euthyroid controls, while H₂O₂ production, hydroperoxide, protein-bound carbonyl and nitrotyrosine levels, and susceptibility to swelling were higher. L-NNA blocked the reperfusion tachycardic response and increased inotropic recovery in hyperthyroid hearts. L-NNA decreased mitochondrial H₂O₂ production and oxidative damage, and increased respiration and tolerance to swelling. Such effects were higher in hyperthyroid preparations. These results confirm the role of mitochondria in ischemia-reperfusion damage, and strongly suggest that NO overproduction is involved in the high mitochondrial dysfunction and the low recovery of hyperthyroid hearts from ischemia-reperfusion. L-NNA also decreased protein content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000 g. This and previous results suggest that the above fraction contains, together with light mitochondria, damaged mitochondria coming from the heaviest fraction, which has the highest cytochrome oxidase activity and capacity to produce H₂O₂. Therefore, we propose that the high mitochondrial susceptibility to swelling, favoring mitochondrial population purification from H₂O₂-overproducing mitochondria, limits hyperthyroid heart oxidative stress.Received 24 March 2004; received after revision 9 June 2004; accepted 5 July 2004     

Inhibition of succinic oxidase activity of beef heart mitochondria by a new fluorescent metabolite,zoanthoxantin

Résumé La zoanthoxantine est un nouveau composé aromatique, très fluorescent, caractérisé par le chromophore 1,3,5,7-tétrazacyclopent[f]azulen. On démontre l'action inhibitrice de ce métabolite sur une préparation submitochondriale de cur de buf et le type d'inhibition en a été déterminé. On envisage, aussi la possiblité d'utiliser la zoanthoxantine comme indicateur moléculaire dans la zone d'inhibition.

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We are indebted to Professor A. Azzi for helpful criticism and discussion.     

Comparative oxidation of erucic and oleic acids by mitochondria isolated from heart auricle of living man]

Mitochondria were isolated from fragments of heart auricles, that were cut off during surgical intracardiac operations. They were incubated with either [14 14C] erucic acid or [10 14C] oleic acid as a control. In the experimental conditions used, the radioactive products soluble in perchloric acid, that are issued from the beta-oxidation reactions in mitochondria, were formed in much lower amounts from erucic acid than from oleic acid. These results show the very low capacity of human heart mitochondria to use directly erucic acid as a substrate for energy requirements, as has been observed before with other animal species. Activation of fatty acids, the preliminary step of their beta-oxidation, was also observed to be very much lower with erucic acid.     

Rapid staining of mitochondria

Riassunto Viene descritta una nuova semplice tecnica per la colorazione rapida dei mitocondri nelle sezioni di tessuti: i pezzi devono essere fissati in formalina, le fettine, dopo sparaffinamento, vengono immerse in una soluzione calda (60°C) di acido cloridrico normale per 3 min e poi colorate con fucsina acida (1%) per 30 sec e con verde luce (1%) per 1–3 min. I mitocondri risaltano intensamente colorati in rosso con una sottile parete colorata in verde.     

Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria

Tyrosine phosphorylation by unidentified enzymes has been observed in mitochondria, with recent evidence indicating that non-receptorial tyrosine kinases belonging to the Src family, which represent key players in several transduction pathways, are constitutively present in mitochondria. The extent of protein phosphorylation reflects a coordination balance between the activities of specific kinases and phophatases. The present study demonstrates that purified rat brain mitochondria possess endogenous tyrosine phosphatase activity. Mitochondrial phosphatases were found to be capable of dephosphorylating different exogenous substrates, including paranitrophenylphosphate, ³²P-poly(Glu-Tyr)_4:1 and ³²P-angiotensin. These activities are strongly inhibited by peroxovanadate, a well-known inhibitor of tyrosine phosphatases, but not by inhibitors of alkali or Ser/Thr phosphatases, and mainly take place in the intermembrane space and outer mitochondrial membrane. Using a combination of approaches, we identified the tyrosine phosphatase Shp-2 in mitochondria. Shp-2 plays a crucial role in a number of intracellular signalling cascades and is probably involved in several human diseases. It thus represents the first tyrosine phosphatase shown to be present in mitochondria.Received 17 May 2004; received after revision 20 July 2004; accepted 26 July 2004     

Magnesium-calcium antagonism in the contraction of arterioles

Zusammenfassung Erhöhung des Mg-Spiegels im Blut hemmt Tonus und Kontraktilität der Widerstandsgefässe im Muskel. Durch Noradrenalin hervorgerufene Verengerung wird gleich stark gehemmt wie die durch Reizung sympathischer Nerven verursachte Kontraktion. Ein Überschuss an Ca⁺⁺ verhindert die blockierende Wirkung des Mg⁺⁺ auf die Kontraktilität, der Tonusverlust der Gefässe wird durch Ca⁺⁺ jedoch nicht rückgängig gemacht. Die antagonistischen Wirkungen von Mg⁺⁺ und Ca⁺⁺ beruhen wahrscheinlich auf deren gegensätzlicher Wirkung auf die elektromechanische Kopplung im Gefässmuskel.

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U.S. Public Health Service International Fellow.     

Glutamine stimulates translation of uncoupling protein 2mRNA

Uncoupling protein 2 (UCP2) belongs to a family of transporters/exchangers of the mitochondrial inner membrane. Using cell lines representing natural sites of UCP2 expression (macrophages, colonocytes, pancreatic beta cells), we show that UCP2 expression is stimulated by glutamine at physiological concentrations. This control is exerted at the translational level. We demonstrate that the upstream open reading frame (ORF1) in the 5’ untranslated region (5’UTR) of the UCP2 mRNA is required for this stimulation to take place. Cloning of the 5’ UTR of the UCP2 mRNA in front of a GFP cDNA resulted in a reporter gene with which GFP expression could be induced by glutamine. An effect of glutamine on translation of a given mRNA has not been identified before, and this is the first evidence for a link between UCP2 and glutamine, an amino acid oxidized by immune cells or intestinal epithelium and playing a role in the control of insulin secretion. Received 26 January 2007; received after revision 16 April 2007; accepted 8 May 2007 C. Hurtaud, C. Gelly: These authors contributed equally to this work.