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The seminal idea that a gas, in this case nitrous oxide, could have a direct effect on pharmacological receptors and thus influence neurotransmission was first suggested in 1981 from clinical work (1,2) and in more detail (3) immediately prior to in vitro experimental evidence (4). The latter work was later confirmed by workers at NIDA (5). That N2O was the first gas to be directly implicated in neurotransmission has also been highlighted elsewhere (6-10). There is now evidence that nitrous oxide is produced endogenously and therefore could also qualify as a gasotransmitter (11,12). While these gasotransmitters may not fit with the criteria for classical neurotransmitters such as acetylcholine, they share several common characteristics amongst themselves, which allow them to be classed together as gasotransmitters (see ref. 2). The gasotransmitters play a major role in physiological and pathological processes such as blood pressure regulation, neurotransmission, inflammatory processes etc. It is worth noting that all four of these gases are also components of air pollution. The 1998 Nobel Prize in Medicine was awarded to Robert Furchgott, Louis Ignarro and Ferid Murad for their research which led to the discovery of nitric oxide as a biological mediator. A class of drugs known as nitrates (such as glyceryl trinitrate), which have been used for many years in the treatment of angina pectoris, produce their beneficial effect through the release and action of nitric oxide.
- Gillman MA, Lichtigfeld FJ. A comparison of the effect of morphine sulphate and nitrous oxide analgesia on chronic pain states in man. J Neurol Sci 45: 41-45, 1981.
- Gillman MA, Lichtigfeld FJ. (1981)The similarity of the action of nitrous oxide and morphine. Pain 10: 110, 1981.
- Gillman MA, Lichtigfeld FJ Nitrous oxide interacts with opioid receptors: More evidence. Anesthesiology 58: 85-86,1983.
- Daras C, Cantrill R, Gillman MA. (3H)Naloxone displacement: evidence for nitrous oxide as opioid receptor agonist. Eur J Pharmacol 89:177-178.
- Ori C., Ford-Rice F and London E.D. Effects of nitrous oxide and halothane on mu and kappa opioid receptors in guinea-pig brain. Anesthesiology 70: 541-544,1989.
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- Gillman MA. Nitrous oxide as neurotransmitter. Lancet 339 : 307;1992.
- Gillman MA. Nitrous oxide, Nitric oxide and neurotransmission. Brit Med J 305: 1368,1992.
- Gillman MA, Lichtigfeld FJ. NO comments. Nature 367: 28;1994.
- Gillman MA. (2004). Discovery of gasotransmission. The Scientist 18:
- Hyun J., Chaudhuri G. and Fakuto JM. The reductive metabolism of nitric oxide in hepatocytes: possible interaction with thiols. Dru. Metab Dispos 27: 1005-09, 1999.
- Einarsdottir O, Caughey WS. Interactions of the anesthetic N2O with bovine heart cytochrome c oxidase. JBiol Chem 263: 9199-9205, 1988.
- Wang R (ed) (2004) Signal Transduction and the Gasotransmitters: NO, CO and H2S in Biology and Medicine. Humana Press, New Jersey, USA.
- Wang R. Two's company, three's a crowd - Can H2S be the third endogenous gaseous transmitter? FASEB Journal 16: 1792-1798,2002.
- Cooke JP. The 1998 Nobel prize in Medicine: clinical implications for 1999 and beyond. Vascular Medicine 4:57-60, 1999.
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