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
Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
,
carbon monoxide
Carbon monoxide (chemical formula CO) is a poisonous, flammable gas that is colorless, odorless, tasteless, and slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...
, and
hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is toxic, corrosive, and flammable. Trace amounts in ambient atmosphere have a characteristic foul odor of rotten eggs. Swedish chemist ...
are accepted as gasotransmitters.
According to in vitro models, gasotransmitters, like other gaseous signaling molecules, may bind to
gasoreceptors and trigger signaling in the cells.
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 fluid
Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the Body (biology), body of an organism. In lean healthy adult men, the total body water is about 60% (60–67%) of the total Human body weight, body weight; it ...
s and
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. 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.
Criteria
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.
Overview
Three candidate 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.
The three gases have similar features and, in theory, participate in shared signaling pathways, although their actions can either be synergistic or antagonistic. Nitric oxide and hydrogen sulfide are highly reactive with numerous molecular targets, whereas carbon monoxide is relatively stable and metabolically inert predominately limited to interacting with ferrous ion complexes within mammalian organisms.
The scope of biological functions are different across biological systems.
Gasotransmitters are under investigation in disciplines such as:
biosensing, immunology, neuroscience, gastroenterology, and many other fields to include pharmaceutical development initiatives.
While biomedical research has received the most attention, gasotransmitters are under investigation throughout biological systems. Many analytical tools have been developed to study gasotransmitters in vitro.
Nitric oxide
The 1998
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
was awarded for the discovery of nitric oxide (NO) as an endogenous signaling molecule. The research emerged in 1980 when NO was first known as the '
endothelium-derived relaxing factor' (EDRF). The identity of EDRF as actually being NO was revealed in 1986 which many consider to mark the beginning of the modern era of gasotransmitter research.
Relative to carbon monoxide and hydrogen sulfide, NO is exceptional due to the fact it is a radical gas. NO is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make NO ideal for a transient
paracrine
In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...
(between adjacent cells) and
autocrine
Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with ...
(within a single cell) signaling molecule.
It is a known bioproduct in almost all types of organisms, ranging from bacteria to plants, fungi, and animal cells. NO is biosynthesized endogenously from
L-arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the ...
by various
nitric oxide synthase (NOS)
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s. Reduction of inorganic nitrate may also serve to make NO. Independent of NOS, an alternative pathway coined the nitrate-nitrite-nitric oxide pathway, elevates NO through the sequential reduction of dietary nitrate derived from plant-based foods such as: leafy greens, such as
spinach
Spinach (''Spinacia oleracea'') is a leafy green flowering plant native to Central Asia, Central and Western Asia. It is of the order Caryophyllales, family Amaranthaceae, subfamily Chenopodioideae. Its leaves are a common vegetable consumed eit ...
and
arugula
Rocket, eruca, or arugula (''Eruca sativa'') is an edible annual plant in the family Brassicaceae used as a leaf vegetable for its fresh, tart, bitter, and peppery flavor. Its other common names include salad rocket and garden rocketFlora of NW ...
, and
beetroot
The beetroot (British English) or beet (North American English) is the taproot portion of a ''Beta vulgaris'' subsp. ''vulgaris'' plant in the Conditiva Group. The plant is a root vegetable also known as the table beet, garden beet, dinner bee ...
. For the human body to generate NO through the nitrate-nitrite-nitric oxide pathway, the reduction of nitrate to nitrite occurs in the mouth by the
oral microbiome.
The production of NO is elevated in populations living at high altitudes, which helps these people avoid
hypoxia by aiding in pulmonary vasculature
vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...
. The
endothelium
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
(inner lining) of
blood vessel
Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
s uses NO to signal the surrounding
smooth muscle
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
to relax, thus resulting in
vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...
and increasing blood flow. NO contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. Humans with
atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
,
diabetes
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
, or
hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
often show impaired NO pathways. In the context of hypertension, the vasodilatory mechanism follows: NO acts through the stimulation of the soluble guanylate cyclase, which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates
protein kinase G, which causes reuptake of Ca
2+ and the opening of calcium-activated potassium channels. The fall in concentration of Ca
2+ ensures that the myosin light-chain kinase (MLCK) can no longer phosphorylate the myosin molecule, thereby stopping the crossbridge cycle and leading to relaxation of the smooth muscle cell.
NO is also generated by phagocytes (
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s,
macrophage
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s, and
neutrophil
Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
s) as part of the human
immune response
An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...
. Phagocytes are armed with inducible nitric oxide synthase (iNOS), which is activated by
interferon-gamma
Interferon gamma (IFNG or IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. ...
(IFN-γ) as a single signal or by
tumor necrosis factor
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
(TNF) along with a second signal. On the other hand,
transforming growth factor-beta (TGF-β) provides a strong inhibitory signal to iNOS, whereas
interleukin
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...
-4 (IL-4) and IL-10 provide weak inhibitory signals. In this way, the immune system may regulate the resources of phagocytes that play a role in inflammation and immune responses. NO is secreted as free radicals in an immune response and is toxic to bacteria and intracellular parasites, including ''
Leishmania
''Leishmania'' () is a genus of parasitic protozoans, single-celled eukaryotic organisms of the trypanosomatid group that are responsible for the disease leishmaniasis. The parasites are transmitted by sandflies of the genus '' Phlebotomus'' ...
'' and
malaria
Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
; the mechanism for this includes DNA damage and degradation of iron sulfur centers into iron ions and
iron-nitrosyl compounds.
Two important biological reaction mechanisms of NO are S-
nitrosation of thiols, and nitrosylation of transition metal ions. S-nitrosation involves the (reversible) conversion of
thiol
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
groups, including
cysteine
Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
residues in proteins, to form S-nitrosothiols (RSNOs). S-
Nitrosation is a mechanism for dynamic, post-translational regulation of most or all major classes of protein. The second mechanism, nitrosylation, involves the binding of NO to a transition metal ion like iron to modulate the normal enzymatic activity of an enzyme such as
cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
. Nitrosylated ferrous iron is particularly stable, as the binding of the nitrosyl ligand to ferrous iron (Fe(II)) is very strong. Hemoglobin is a prominent example of a heme protein that may be modified by NO by multiple pathways.
There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. These include oxidation of iron-containing proteins such as
ribonucleotide reductase
Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase, is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of the ribos ...
and
aconitase
Aconitase (aconitate hydratase; ) is an enzyme that catalyses the stereochemistry, stereo-specific isomerization of citrate to isocitrate via ''cis''-aconitate in the tricarboxylic acid cycle, a non-redox-active process.
Image:Citrate wpmp.p ...
, activation of the soluble
guanylate cyclase, ADP ribosylation of proteins, protein sulfhydryl group
nitrosylation, and iron regulatory factor activation. NO has been demonstrated to activate
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...
in peripheral blood mononuclear cells, an important transcription factor in iNOS gene expression in response to inflammation.
Carbon monoxide
Carbon monoxide (CO) is produced naturally throughout phylogenetic kingdoms. In mammalian physiology, CO is an important
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
with beneficial roles such as reducing inflammation and
blood vessel relaxation.
Mammals maintain a baseline
carboxyhemoglobin
Carboxyhemoglobin (carboxyhaemoglobin BrE) (symbol COHb or HbCO) is a stable complex (chemistry), complex of carbon monoxide and hemoglobin (Hb) that forms in red blood cells upon contact with carbon monoxide. Carboxyhemoglobin is often mistaken ...
level even if they do not breathe any CO fumes.
In mammals, CO is produced through many enzymatic and non-enzymatic pathways. The most extensively studied source is the catabolic action of
heme oxygenase
Heme oxygenase, or haem oxygenase, (HMOX, commonly abbreviated as HO) is an enzyme that catalyzes the degradation of heme to produce biliverdin, ferrous iron, and carbon monoxide.
There are many heme degrading enzymes in nature. In general, on ...
(HMOX) which has been estimated to account for 86% of endogenous CO production. Other contributing sources include: the microbiome,
cytochrome P450 reductase, human
acireductone dioxygenase,
tyrosinase
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper–Mason pathway. Firstly, the hydroxy ...
,
lipid peroxidation,
alpha-keto acids, and other oxidative mechanisms. Similarly, the velocity and catalytic activity of HMOX can be enhanced by a plethora of dietary substances and xenobiotics to increase CO production.
The biomedical study of CO traces back to
factitious airs in the 1790s when
Thomas Beddoes
Thomas Beddoes (13 April 176024 December 1808) was an English physician and scientific writer. He was born in Shifnal, Shropshire and died in Bristol fifteen years after opening his medical practice there. He was a reforming practitioner and te ...
,
James Watt
James Watt (; 30 January 1736 (19 January 1736 OS) – 25 August 1819) was a Scottish inventor, mechanical engineer, and chemist who improved on Thomas Newcomen's 1712 Newcomen steam engine with his Watt steam engine in 1776, which was f ...
,
James Lind
James Lind (4 October 1716 – 13 July 1794) was a Scottish physician. He was a pioneer of naval hygiene in the Royal Navy. By conducting one of the first ever clinical trials, he developed the theory that citrus fruits cured scurvy.
Lind ...
, and many others investigated beneficial effects of
hydrocarbonate (water gas) inhalation. Following
Solomon Snyder's first report that CO is a normal neurotransmitter in 1993,
CO has received significant clinical attention as a biological regulator. Unlike NO and , CO is an inert molecule with remarkable chemical stability capable of diffusing through membranes to exert its effects locally and in distant tissues. CO has been shown to interact with molecular targets including
soluble guanylyl cyclase, mitochondrial oxidases,
catalase
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting ...
,
nitric oxide synthase,
mitogen-activated protein kinase
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflamma ...
,
PPAR gamma,
HIF1A
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 ( HIF-1) that is encoded by the ''HIF1A'' gene. The Nobel Prize in Physiology or Medicine 2019 was awa ...
,
NRF2
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the ''NFE2L2'' gene. NRF2 is a basic leucine zipper (bZIP) protein that may regu ...
,
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
s,
cystathionine beta synthase
Cystathionine-β-synthase, also known as CBS, is an enzyme () that in humans is encoded by the ''CBS'' gene. It catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine:
: L-serine + L-homocysteine \rightlef ...
, and numerous other functionalities. It is widely accepted that CO primarily exerts its effects in mammals primarily through interacting with
ferrous ion complexes such as the
prosthetic
In medicine, a prosthesis (: prostheses; from ), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through physical trauma, disease, or a condition present at birth (Congenital, congenital disord ...
heme
Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...
moiety of
hemoprotein
A hemeprotein (or haemprotein; also hemoprotein or haemoprotein), or heme protein, is a protein that contains a heme prosthetic group. They are a very large class of metalloproteins. The heme group confers functionality, which can include oxygen ...
s.
Aside from Fe
2+ interactions, CO may also interact with zinc within metalloproteinases, non-metallic histidine residues of certain ion channels, and various other metallic targets such nickel and molybdenum.
Hydrogen sulfide
Hydrogen sulfide () has important signaling functions in mammalian physiology. The gas is produced
enzymatically
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as produc ...
by
cystathionine beta-synthase and
cystathionine gamma-lyase
The enzyme cystathionine γ-lyase (EC 4.4.1.1, CTH or CSE; also cystathionase; systematic name L-cystathionine cysteine-lyase (deaminating; 2-oxobutanoate-forming)) breaks down cystathionine into cysteine, 2-oxobutanoate ( α-ketobutyrate), an ...
, endogenous non-enzymatic reactions, and may also be produced by the
microbiome
A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably wel ...
. Eventually the gas is converted to sulfite in the
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
by thiosulfate reductase, and the sulfite is further oxidized to
thiosulfate
Thiosulfate ( IUPAC-recommended spelling; sometimes thiosulphate in British English) is an oxyanion of sulfur with the chemical formula . Thiosulfate also refers to the compounds containing this anion, which are the salts of thiosulfuric acid, ...
and
sulfate
The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...
by
sulfite oxidase
Sulfite oxidase () is an enzyme in the mitochondria of all eukaryotes, with exception of the yeasts. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ...
. The sulfates are excreted in the urine.
acts as a relaxant of
smooth muscle
Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...
and as a
vasodilator
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...
.
Though both NO and have been shown to relax blood vessels, their mechanisms of action are different: while NO activates the enzyme
guanylyl cyclase
Guanosine monophosphate (GMP), also known as 5′-guanidylic acid or guanylic acid ( conjugate base guanylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of th ...
, activates
ATP-sensitive potassium channel
An ATP-sensitive potassium channel (or KATP channel) is a type of potassium channel that is gated by intracellular nucleotides, ATP and ADP. ATP-sensitive potassium channels are composed of Kir6.x-type subunits and sulfonylurea receptor (S ...
s in smooth muscle cells. Researchers are not clear how the vessel-relaxing responsibilities are shared between NO and . However, there exists some evidence to suggest that NO does most of the vessel-relaxing work in large vessels and is responsible for similar action in smaller blood vessels.
deficiency can be detrimental to the vascular function after an
acute myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom is retr ...
(AMI). therapy reduces myocardial injury and reperfusion complications.
Due to its effects similar to NO (without its potential to form
peroxides
In chemistry, peroxides are a group of compounds with the structure , where the R's represent a radical (a portion of a complete molecule; not necessarily a free radical) and O's are single oxygen atoms. Oxygen atoms are joined to each other and ...
by interacting with
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
), is now recognized as potentially protecting against cardiovascular disease.
Recent findings suggest strong cellular crosstalk of NO and ,
demonstrating that the vasodilatatory effects of these two gases are mutually dependent. Additionally, reacts with intracellular
S-nitrosothiols to form the smallest S-nitrosothiol (HSNO), and a role of in controlling the intracellular S-nitrosothiol pool has been suggested.
Gasotransmitter candidates
Some
gaseous signaling molecules may be a gasotransmitter, notably
methane
Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The abundance of methane on Earth makes ...
and
cyanide
In chemistry, cyanide () is an inorganic chemical compound that contains a functional group. This group, known as the cyano group, consists of a carbon atom triple-bonded to a nitrogen atom.
Ionic cyanides contain the cyanide anion . This a ...
. There is ongoing controversy about the strict criteria for gasotransmitters. Some researchers have proposed use of the term ''small molecule signaling agent'', while others have proposed to relax the criteria to include other gases, such as
oxygen
Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
as an essential gasotransmitter, similar to that of
essential amino acids
An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life forms ...
.
References
External links
European Network on Gasotransmitters (ENOG)
{{Neurotransmitters
Neurotransmitters
Gaseous signaling molecules