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E Benoit

Publications and source records attributed to E Benoit.

35 records · Page 2Linked to original sources
PubMed1987

Electrophysiological studies of the effects of the general anaesthetic etomidate on frog myelinated nerve fibre.

The effects of the general anaesthetic etomidate (0.1 to 1 mM) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, etomidate reversibly decreased the amplitude of the action potential. The action potential block, induced by the drug, was reversed by increasing the membrane potential. Etomidate rapidly and reversibly blocked the Na current with an apparent dissociation constant of 0.6 mM. In the presence of the drug, the steady-state inactivation-voltage curve of the Na current was shifted towards negative voltages. The block of Na current by etomidate was partially removed by repetitive depolarization preceded by a 50 ms period of hyperpolarization. In contrast, the block was enhanced when the repetitive depolarization was not preceded by hyperpolarization. This suggests that Na channels were preferentially blocked by the drug in the inactivated state. The K current was reversibly blocked by etomidate with an apparent dissociation constant of 0.2 mM. In the presence of the drug, the K current showed an apparent fast inactivation suggesting that K channels were blocked in the open state. We conclude that at higher concentrations than those attainable in the mammalian brain following single anaesthetic doses the general anaesthetic etomidate has a "local anaesthetic-like' action on the peripheral nervous system.

Action Potentials↗
PubMed1987

Properties of maintained sodium current induced by a toxin from Androctonus scorpion in frog node of Ranvier.

1. The effects of toxin II from scorpion Androctonus australis Hector (AaH II) on the Na current of frog myelinated nerve fibres were analysed under voltage-clamp conditions. 2. Like other alpha-scorpion toxins and Anemonia toxin II, AaH II both increased the inactivation time constants of peak Na current and induced a non-inactivatable Na current (maintained current). 3. In the presence of AaH II, the slope of the maintained conductance-voltage curve was less steep than that corresponding to the peak conductance and the maintained current reversed at a voltage about 20 mV more negative than the peak current. 4. When the peak current was inactivated by pre-depolarizations, 'on' and 'off' relaxation kinetics of the maintained current were an exponential function whose time constant changed with voltage in a bell-shaped manner. At 0 mV, the time constant was about 10 ms. 5. The effects of AaH II could be decomposed into fast effects (increase in inactivation time constants of the peak current) which developed within about 5 s and slow effects (increase in maintained current and changes in initial amplitudes of fast and slow phases of peak current inactivation) which developed within about 30 s. 6. These two types of AaH II effects could be completely removed by conditioning depolarizations giving rise to outward currents. 7. A model is proposed in which the binding of the toxin with its receptor is modulated by membrane potential and internal cations, the appearance of the maintained current is modulated by the environment of channels and the change in inactivation time constants is modulated by membrane potential. The maintained current would correspond to the transformation of a fraction of channels into a non-inactivable (late) form.

Animals↗
PubMed1987

Interactions of guanidinium ions with sodium channels in frog myelinated nerve fibre.

1. The effects of external guanidinium ions on fast and slow inactivating currents flowing through sodium channels of the frog myelinated nerve fibre (Benoit, Corbier & Dubois, 1985) were analysed under voltage-clamp conditions. 2. When external sodium ions were partially replaced by guanidinium ions, the fast inactivating current was preferentially reduced and was absent in a solution containing guanidinium ions as the only external permeant cations. The inactivation time constants of both fast and slow currents were not significantly modified by the replacement of sodium ions by guanidinium ions. 3. Substitution of guanidinium ions for all sodium ions shifted the steady-state inactivation curve of the slow inactivating current towards positive voltages. 4. The voltage dependence of the activation of fast and slow inactivating currents was shifted towards positive voltages by guanidinium ions. Moreover, the activation-voltage curve of the slow inactivating current, which was biphasic under control conditions, was monophasic when guanidinium ions were substituted for all sodium ions. 5. Whereas the slow inactivating current could be carried by guanidinium ions, these cations were not only impermeant through the sodium channels which give rise to the fast inactivating current but also blocked this type of channel with an apparent dissociation constant of 49 mM. 6. It is concluded that guanidinium appears to be an efficient tool for further separating the two types of inactivating current and studying the properties of the slow inactivating current. These results are consistent with the suggestion that there are two types of sodium channels, fast and slow, with guanidinium ions being permeant only through the slow ones.

Action Potentials↗
PubMed1987

Pharmacokinetics of albendazole administered by an intraruminal pulse release electronic device in cattle.

Albendazole was administered to 12 young Charolais cattle, 300 kg bodyweight, using an intraruminal pulse release electronic device. The device released 2 g albendazole three times at 31 day intervals. The kinetic study of two main metabolites of albendazole in all animals at the time of each release showed that on 36 occasions the devices worked at the expected time; the mean kinetic profiles were nearly identical at first, second and third release. A good repeatability was generally also noticed for each animal individually; the bioavailability of the drug did not seem to be different from that obtained after administration of albendazole as an oral drench.

Administration, Oral↗
PubMed1986

Toxin I from the snake Dendroaspis polylepis polylepis: a highly specific blocker of one type of potassium channel in myelinated nerve fiber.

Toxin I from the venom of the black mamba snake Dendroaspis polylepis polylepis specifically blocks one component of the K-current (IKf1) in the frog node of Ranvier, with a high affinity (Kd = 4 X 10(-10) M) without significantly affecting either the others components of the K current (IKf2 and IKs) or the Na-current. Moreover, for toxin concentrations corresponding to 10- or 100-fold the Kd value, the block was almost irreversible.

Animals↗
PubMed1986

Effects of ciguatoxin on current and voltage clamped frog myelinated nerve fibre.

The effects of 0.25 X 10(-9) and 1.25 X 10(-9) g/ml of purified ciguatoxin (CgTX) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, CgTX induced spontaneous action potentials at a frequency of about 100 Hz, which were reversible upon removal of the toxin. Under voltage clamp conditions, CgTX modified neither linear leakage and capacity currents nor K current, but reversibly induced a maintained (late) inward current (IL) during long lasting depolarizations. IL, as well as the peak Na current, was suppressed by tetrodotoxin (300 nM). The steady-state inactivation curve of the Na current showed that a fraction of the current (corresponding to IL) did not inactivate. IL activated and reversed at voltages about 30 mV more negative than the peak Na current (recorded under control conditions or in the presence of CgTX). During a given depolarizing pulse, the amplitude of IL depended on the holding potential. IL was about three times greater when the holding potential was -70 mV rather than -120 mV. We conclude that CgTX specifically interacts with and modifies Na channels. We also conclude that the effects of CgTX depend on membrane potential.

Animals↗
PubMed1986

Mechanism of action of ketamine in the current and voltage clamped myelinated nerve fibre of the frog.

The effects of the general anaesthetic ketamine, on the frog isolated node of Ranvier, were studied under current and voltage clamp conditions. Ketamine (0.5 and 1 mM) reversibly decreased the amplitude of the action potential and increased both the duration of the action potential and the threshold potential. When the K current was blocked, spontaneous action potentials appeared after washout of the drug. Ketamine rapidly blocked the Na current and more slowly modified a fraction of Na channels (about 10%) to give rise to a non-inactivatable (late) Na current. After washout of the drug, the block reversed more rapidly than the ketamine-induced late Na current disappeared. Steady-state outward, peak Na and ketamine-induced late Na currents were rapidly and reversibly blocked by ketamine with an apparent dissociation constant of 0.7 mM. Both peak Na and ketamine-induced late Na currents were reversibly blocked by procaine.

Action Potentials↗
PubMed1985

Cooperativity of tetrodotoxin action in the frog node of Ranvier.

The steady state effects and rates of action of tetrodotoxin (TTX) on sodium current were studied in the voltage clamped frog node of Ranvier. Inactivation of the sodium current was separated into fast and slow phases. Both phases were assumed to correspond to two different currents (fast and slow) flowing through fast and slow channels (Benoit et al. 1985). The dose-response curve of the steady state effect of tetrodotoxin on the fast current was sigmoid. An analysis of this effect in double logarithmic coordinates gave a Hill coefficient of 1.74. The rates of tetrodotoxin action on the fast current were determined by the reversible reduction of the peak current recorded at a potential (+20 mV) at which the slow current was relatively small. After an initial delay, the onset of TTX effect followed an exponential function of time whose constant decreased with increasing tetrodotoxin concentrations. Expressed as the time corresponding to a reduction of 2% of the current, the delay (delta t2%) increased from about 100 ms with 300 nM-TTX to about 30 s with 1 nM-TTX. When tetrodotoxin was removed, the offset developed quasi-instantaneously and followed an exponential function of time whose constant was independent of the toxin concentration. Both steady state and rates of tetrodotoxin effects could be fitted well if one assumed that the block of one fast channel occurred after binding of two TTX molecules to two cooperative sites.

Animals↗
PubMed1985

Evidence for two transient sodium currents in the frog node of Ranvier.

Na current (INa) was monitored in isolated voltage-clamped frog nodes of Ranvier in order to analyse the pharmacological and kinetic properties of fast and slow phases of inactivation. Niflumic acid (0.1-10 mM) and tetrodotoxin (0.3-30 nM) did not alter fast and slow inactivation time courses but preferentially reduced the amplitude of the fast phase of inactivation. The block of both phases of inactivation by niflumic acid and tetrodotoxin was well described if one assumed that more than one molecule of drug reacted with one channel. Fast and slow currents, corresponding respectively to fast and slow phases of inactivation, reversed at different potentials, had different threshold voltages of activation and the slopes of their steady-state inactivation curves were different. The recovery from inactivation of the compound INa could be described by the sum of two exponentials (plus a delay) corresponding respectively to fast and slow currents. When calculated from INa recorded without and with niflumic acid or tetrodotoxin, the slow current activated about three times more slowly than the fast current. Large prehyperpolarizations delayed both the activation and the inactivation of the fast current but only the activation of the slow current. Lowering the temperature decreased the fast current but increased the slow current. We conclude that the inactivatable Na current of the nodal membrane is made up of two components (INa,f and INa,s) corresponding to two different and interconvertible forms of the Na channel.

Action Potentials↗
PubMed1985

Radioimmunoassay of 19 nor testosterone. Evidence of its secretion by the testis of the stallion.

Antiserum has been raised in rabbits treated with a 19 nor testosterone-hemisuccinate-bovine-serum-albumin conjugate and used for the development of a specific RIA of plasma 19 nor testosterone. Plasma samples are drawn from testicular and jugular veins of stallions during castration under general anesthesia. Results demonstrate a testicular secretion of 19 nor testosterone and a stress inhibition of this secretion correlatively with stress inhibition of testosterone secretion.

Animals↗
PubMedDate not supplied

Comparative pharmacokinetics of netobimin and albendazole in the one-humped camel (Camelus dromedarius).

Netobimin and albendazole were administered orally to camels (n = 5 + 5) at molecular equivalent dosages, 15.8 and 10.0 mg/kg body wt, respectively. The plasma profiles of the two main metabolites were investigated for 54 h by high performance liquid chromatography. The metabolism and the disposition of both anthelmintics in camels were similar to sheep rather than to cattle. These results indicate that netobimin and albendazole are likely to be excellent anthelmintics for camels.

Albendazole↗
PubMedDate not supplied

Specific and enantioselective sulfoxidation of an aryl-trifluoromethyl sulfide by rat liver cytochromes P-450.

Evidence based on thermal stability and enzyme inhibition data suggests that the sulfoxidation of the drug toltrazuril by rat liver microsomes is catalyzed by different cytochromes P-450. Pretreatment of rats by different inducers--phenobarbital, 3-methylcholanthrene, dexamethasone, and triacetyloleandomycin--results in a 2.1-, 2.6-, 2.9-, and 1.8-fold increase, respectively, in the rate of sulfoxidation. The highest increase (8.4-fold) was observed after treatment of microsomes from triacetyloleandomycin-treated animals by potassium ferricyanide. Castration and aging also modify the sulfoxidase activity. The relative rate of formation of the two toltrazuril enantiomers [(A)- and (B)-sulfoxides] depends on the source of the microsomes, suggesting that different cytochromes P-450 have different stereoselectivities.

Animals↗