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Concept
Gasotransmitter
Summary
Gasotransmitters is a class of neurotransmitters. The molecules are distinguished from other bioactive endogenous gaseous signaling molecules based on a need to meet distinct characterization criteria. Currently, only nitric oxide, carbon monoxide, and hydrogen sulfide are accepted as gasotransmitters.
The name gasotransmitter is not intended to suggest a gaseous physical state such as infinitesimally small gas bubbles; the physical state is dissolution in complex body fluids and cytosol. 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.
The terminology and characterization criteria of “gasotransmitter” were first introduced in 2002. For one gas molecule to be categorized as a gasotransmitter, all of the following criteria should be met.
It is a small molecule of gas;
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;
It is endogenously and enzymatically generated and its production is regulated;
It has well defined and specific functions at physiologically relevant concentrations. Thus, manipulating the endogenous levels of this gas evokes specific physiological changes;
Functions of this endogenous gas can be mimicked by its exogenously applied counterpart;
Its cellular effects may or may not be mediated by second messengers, but should have specific cellular and molecular targets.
The current "trinity" of gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide, have ironically been discarded as useless toxic gases throughout history. These molecules are a classic example of dose-dependent hormesis such that low-dose is beneficial whereas absence or excessive dosing is toxic.
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