New Observations on the Mechanism of Pressure-Anesthetic Interactions

Smith, E. B.; Bowser-Riley, F.; Daniels, Stephen R.

doi:10.1007/978-1-4684-5033-0_28

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…A preliminary communication of some of these results has been made to the Physiological Society and to the Third International Conference on Molecular and Cellular Mechanisms of Anaesthesia (Smith et al, 1986 (Anthony Pratt & Co. Ltd., Surrey; working pressure 400 bar) equipped with full environmental control (temperature, oxygen partial pressure, effluent gases etc.). Helium, in the presence of 1 bar oxygen, was used for all compressions, with a compression rate of 3 bar min1.…”

Section: Introductionmentioning

confidence: 99%

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Bowser-Riley¹,

Daniels²,

Smith³

1988

British J Pharmacology

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1 The effects of a variety of structural isomers of the centrally acting muscle relaxant mephenesin on the high pressure neurological syndrome have been investigated. Threshold pressures for the onset of the behavioural signs, tremors and convulsions, were established. The effects of these compounds on the response to pressure were also compared with their ability to antagonize the convulsive action of strychnine. 2 The dose-response relationships for strychnine and picrotoxin were investigated at fixed pressures. Additionally, the dose-response relationship of strychnine, in the presence of mephenesin, at pressure was investigated. 3 All the isomers of mephenesin protected against the effects of both pressure and strychnine. The relative potency was found to be identical with respect to both. Mephenesin was clearly the most effective; it raised the threshold pressure for tremors by 2.5 times, that for convulsions elicited by pressure by 1.5 and the ED30 for strychnine convulsions by 1.6 times. Strychnine was found to be strictly additive with pressure whereas picrotoxin exhibited gross deviations from additivity. Mephenesin ameliorated the combined effects of pressure and strychnine equally. 4 The marked dependence on structure of the anticonvulsant activity of the mephenesin isomers can be interpreted as evidence that pressure acts not by some general perturbation of the membranes of excitable cells but rather via some specific interaction. The finding that strychnine and pressure are strictly additive supports the idea of specificity and also indicates that they may share a common mechanism in the production of convulsions. By analogy with the established mechanism of action of strychnine, it is suggested that the hyperexcitability associated with pressure might arise from an action on glycine-mediated inhibitory processes.

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Section: Introductionmentioning

confidence: 99%

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Bowser-Riley¹,

Daniels²,

Smith³

1988

British J Pharmacology

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“…There are several reports showing that pressure did not antagonize anesthesia in freshwater shrimp, Gammarus pulex (Smith et al, 1984(Smith et al, , 1986 and in Caenorhabditis elegans (Eckenhoff and Yang, 1994). These negative reports indicate that the pressure effects on living creatures are not due to the pain and discomfort caused by high pressure and that the biphasic effect of pressure, separated by the temperature at the maximum activity (Ueda et al, 1994) where high pressure decreases the biological activities at the temperatures below that gives the maximum activity, may also be operative in the activity of living creatures.…”

Section: Discussionmentioning

confidence: 99%

Does Pressure Antagonize Anesthesia? High-Pressure Stopped-Flow Study of Firefly Luciferase and Anatomy of Initial Flash

Ueda

Minami

Matsuki

et al. 1999

Biophysical Journal

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The antagonizing effect of high pressure against anesthesia is well known. With purified firefly luciferase, however,. Biophys. J. 60:1309-1314) reported that high pressure did not affect the initial flash intensity. Firefly luciferase emits a burst of light when the substrates luciferin and ATP are added in the presence of O2. The light intensity decays rapidly and the weak light lasts for hours. The initial flash is a transient event and is not in a steady state. The steady state is represented by the slope of the linear part of the integral of the light output. The present study used a high-pressure stopped-flow system to compare the pressure effects on the initial flash intensity and the steady-state light intensity. The flash intensity did not change by the application of hydrostatic pressure in the presence or absence of chloroform or 1-octanol. In contrast, high pressure increased the steady-state light intensity. The application of 12 MPa pressure increased the steady-state light intensity of firefly luciferase inhibited by 5 mM chloroform or 0.7 mM 1-octanol by 19.7% and 18.8%, respectively. When analyzed by the rapid reaction kinetics of the transition state theory, the initial peak intensity represents the total amount of active enzyme and is unrelated to the reaction rate. Anesthetics inhibited the initial flash by unfolding the protein, thereby decreasing the concentration of the active enzyme. Pressure affected the steady-state light intensity by changing the reaction rates.

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“…That large pressures (of the order of 10 MPa) will antagonize general anaesthesia [38] led to a theory of general anaesthesia that assumed that anaesthetics and pressure acted at a common site and via a common mechanism [47]. More recently it was observed that species diat do not use glycine as a neurotransmitter do not exhibit pressure reversal of anaesthesia [72] and that pressure, far from acting in a non-specific manner, appears to act in a highly selective way [10,11,71]. At the level of the neurotransmitter receptor-ion channel complex, it has been shown that the kainate channel is unaffected by pressure but that the glycine channel is highly pressure sensitive [16,69].…”

Section: Discussionmentioning

confidence: 99%

Effects of General Anaesthetics on Ligand-Gated Ion Channels

Daniels¹,

Smith²

1993

British Journal of Anaesthesia

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The site at which anaesthetics act within the central nervous system (CNS) has been the subject of research for almost 100 years. Most success has been obtained in defining the physical nature of the site [70]. For example, the well established correlation of anaesthetic potency to fat solubility indicates that the site of action is hydrophobic. Research using anaesthetics with unusual solubility properties (sulphur hexafluoride and carbon tetrafluoride) failed to provide support for the alternative hypothesis that interaction within the aqueous phase of the CNS was responsible for anaesthesia [45,46]. It is now generally agreed that interaction at a hydrophobic site is involved, but debate continues as to whether or not this is within the membrane lipids or at a hydrophobic region within specific proteins. Evidence for the latter view has been provided by the fact that bacterial and firefly luciferases are sensitive to anaesthetics with potency ratios comparable to those of mammalian anaesthesia [21, 22, 32, 42, 43]. However, there is no evidence for a substance related to the luciferases within the mammalian CNS and for the protein model of general anaesthesia to be advanced such a target site must be identified. General anaesthetics may affect signal transmission by altering action potential propagation or synaptic transmission or, indeed, both. At clinically relevant concentrations, general anaesthetics appear primarily to affect synaptic processes [5, 53, 58-61], although impulse conduction in small unmyelinated fibres is reduced [4]. There is some evidence that anaesthetics may inhibit neurotransmitter release also [56], which if it were to occur at an excitatory synapse could produce the necessary depression of synaptic transmission. Anaesthetics also have effects on the postsynaptic neurotransmitter receptor/ion channel complex. Much of the early work concentrated on the nicotinic acetylcholine receptor as a model for ligand-gated ion channels in general. However, attention is now being devoted to the receptors activated by excitatory amino acids, which probably form the majority of the fast excitatory synapses in the CNS, and to the principal inhibitory receptors, activated by yaminobutyric acid (GABA) and glycine.

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New Observations on the Mechanism of Pressure-Anesthetic Interactions

Cited by 5 publications

References 23 publications

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Does Pressure Antagonize Anesthesia? High-Pressure Stopped-Flow Study of Firefly Luciferase and Anatomy of Initial Flash

Effects of General Anaesthetics on Ligand-Gated Ion Channels

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