Gaseous signaling molecules

Gaseous signaling molecules are gaseous molecules that are either synthesised internally (endogenously) in the organism, tissue or cell or are received by the organism, tissue or cell from outside (say, from the atmosphere or hydrosphere, as in the case of oxygen) and that are used to transmit chemical signals which induce certain physiological or biochemical changes in the organism, tissue or cell. The term is applied to, for example, oxygen, carbon dioxide, nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, nitrous oxide, hydrogen cyanide, ammonia, methane, hydrogen, ethylene etc.

Many, but not all, gaseous signaling molecules are called gasotransmitters.

Gasotransmitters is a subfamily of endogenous molecules of gases or gaseous signaling molecules, including NO, CO, H2S.[1] 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.[2][3][4] In vitro experiments confirmed these observations[5] which were replicated at NIDA later.[6]

The terminology and characterization criteria of “gasotransmitter” were firstly introduced in 2002.[7] For one gas molecule to be categorized as a gasotransmitters, all of the following criteria should be met.[8][7]

  1. It is a small molecule of gas;
  2. 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;
  3. It is endogenously and enzymatically generated and its production is regulated;
  4. It has well defined and specific functions at physiologically relevant concentrations. Thus, manipulating the endogenous levels of this gas evokes specific physiological changes;
  5. Functions of this endogenous gas can be mimicked by its exogenously applied counterpart;
  6. 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.


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