Species variation and the mechanism of pressure–anaesthetic interactions

The mechanism of general anaesthesia has proved difficult to elucidate (see ref. 1 for a review), although the relative potencies of anaesthetic agents have been used to establish that the site at which anaesthetics act is hydrophobic in nature2. One further clue to their mode of action is that the effects of anaesthetics on vertebrates can be eliminated by pressures of ∼100 atm (refs 3, 4). However, the effects of anaesthetics are not always reversed in model systems, where there is evidence that the pattern of pressure reversal varies significantly5–10. We now find that pressure fails to reverse the effects of anaesthetics on the freshwater shrimp (Gammarus pulex), although the sensitivity of these crustaceans to anaesthetics is comparable with that of higher animals. This is hard to reconcile with traditional bio-physical mechanisms and indicates that anaesthetics may act at a specific protein site rather than having a general effect on cell membranes. The pharmacology of pressure in mammals seems to be more similar to that of strychnine than of any other central stimulant11. As glycine, whose action is blocked by strychnine, is absent as a neurotransmitter in the arthropod central nervous system, we believe that this substance may be involved in determining pressure–anaesthetic interactions in vertebrates.

[1]  Macdonald Ag,et al.  Interaction between halothane and hydrostatic pressure. , 1970 .

[2]  F. Johnson,et al.  Pressure reversal of the action of certain narcotics , 1942 .

[3]  R A Smith,et al.  Physicochemical Approaches to the Mode of Action of General Anesthetics , 1972, Anesthesiology.

[4]  G. Johnston.  Neuropharmacology of amino acid inhibitory transmitters. , 1978, Annual review of pharmacology and toxicology.

[5]  E. Florey.  Comparative physiology: transmitter substances. , 1961, Annual review of physiology.

[6]  K. Meyer.  Contributions to the theory of narcosis , 1937 .

[7]  E. B. Smith.  The biological effects of high pressures: underlying principles. , 1984, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[8]  F. Johnson,et al.  Hydrostatic pressure reversal of narcosis in tadpoles. , 1950, Science.

[9]  J. Trudell,et al.  Effects of pressure and anesthetics on conduction and synaptic transmission. , 1975, The Journal of pharmacology and experimental therapeutics.

[10]  W. D. M. PATON,et al.  Pressure Reversal of Anaesthesia , 1971, Nature.

[11]  N. P. Franks,et al.  Molecular mechanisms of general anaesthesia , 1982, Nature.

[12]  M. Halsey,et al.  Effects of high pressure on the central nervous system. , 1982, Physiological reviews.

[13]  P. B. Bennett,et al.  Anesthetic antagonism of the effects of high hydrostatic pressure on locomotory activity of the brine shrimp Artemia. , 1983, Comparative biochemistry and physiology. A, Comparative physiology.

[14]  A. Cherkin,et al.  Temperature Dependence of Anesthesia in Goldfish , 1964, Science.

[15]  K. Miller,et al.  Animals at Very High Pressures of Helium and Neon , 1967, Science.

[16]  K. Miller,et al.  Site of Action of General Anaesthetics , 1965, Nature.

[17]  W. Paton,et al.  THE EFFECTS OF HIGH PRESSURE HELIUM AND NITROGEN ON THE RELEASE OF ACETYLCHOLINE FROM THE GUINEA‐PIG ILEUM , 1979, British journal of pharmacology.

[18]  F. Bowser-Riley.  Mechanistic studies on the high pressure neurological syndrome. , 1984, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[19]  Henry Eyring,et al.  The kinetic basis of molecular biology , 1954 .

[20]  H. Little,et al.  EFFECTS OF KETAMINE AND OF HIGH PRESSURE ON THE RESPONSES TO γ‐AMINOBUTYRIC ACID OF THE RAT SUPERIOR CERVICAL GANGLION in vitro , 1982, British journal of pharmacology.

[21]  R A Smith,et al.  Pressure antagonism of anaesthetic-induced conduction failure in frog peripheral nerve. , 1976, British journal of anaesthesia.

[22]  H. Gerschenfeld,et al.  Chemical transmission in invertebrate central nervous systems and neuromuscular junctions. , 1973, Physiological reviews.