Gasotransmitters is a family of endogenous molecules of gases or gaseous signaling molecules, including NO, CO, H2S, and others. These particular gases share many common features in their production and function but carry on their tasks in unique ways, which differ from classical signaling molecules, in the human body. The first suggestion that a gas had a direct action at pharmacological receptors and thereby acting as a neurotransmitter was first suggested in 1981 from clinical work with nitrous oxide (1,2,3). In vitro experiments confirmed these observations (4) which were replicated at NIDA later(5).
The terminology and characterization criteria of “gasotransmitter” were firstly introduced in 2002 (see ref. 14). For one gas molecule to be categorized as a gasotransmitters, all of the following criteria should be met (see ref. 13 &14). (i) It is a small molecule of gas; (ii) It is freely permeable to membranes. As such, its effects do not rely on the cognate membrane receptors. It can have endocrine, paracrine, and autocrine effects. In their endocrine mode of action, for example, gasotransmitters can enter the blood stream; be carried to remote targets by scavengers and released there, and modulate functions of remote target cells; (iii) It is endogenously and enzymatically generated and its production is regulated; (iv) It has well defined and specific functions at physiologically relevant concentrations. Thus, manipulating the endogenous levels of this gas evokes specific physiological changes; (v) Functions of this endogenous gas can be mimicked by its exogenously applied counterpart; (vi) Its cellular effects may or may not be mediated by second messengers, but should have specific cellular and molecular targets.
In 2011, a European Network on Gasotransmitters (ENOG) was formed. The aim of the network is to promote research on NO, CO and H2S in order to better understand the biology of gasotransmitters and to unravel the role of each mediator in health and disease. Moreover, the network aims to contribute to the translation of basic science knowledge in this area of research into therapeutic or diagnostic tools.
- Gillman MA, Lichtigfeld FJ (January 1981). "A comparison of the effects of morphine sulphate and nitrous oxide analgesia on chronic pain states in man". J. Neurol. Sci. 49 (1): 41–5. doi:10.1016/0022-510X(81)90186-6. PMID 7205318.
- Gillman MA, Lichtigfeld FJ (February 1981). "The similarity of the action of nitrous oxide and morphine". Pain 10 (1): 110. PMID 7232008.
- Gillman MA, Lichtigfeld FJ (May 1983). "Nitrous oxide interacts with opioid receptors: more evidence". Anesthesiology 58 (5): 483–4. PMID 6301312.
- 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.
- Allen A. US science journal ignores S.A. find. The Star 13 May 1992: 8.
- 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.
- Garthwaite J. (2008). Concepts of neural nitric oxide-mediated transmission. European Journal of Neuroscience 27: 2783-2802.
- Papapetropoulos A, Pyriochou A, Altaany Z, Yang G, Marazioti A, Zhou Z, Jeschke MG, Branski LK, Herndon DN, Wang R, Szabó C . Hydrogen sulfide is an endogenous stimulator of angiogenesis. PNAS 2009.