Gaseous signaling molecules

Gaseous signaling molecules are

Historically, the study of gases and physiological effects was categorized under factitious airs.

The biological roles of each of the gaseous signaling molecules are outlined below.

Gasotransmitters

Gasotransmitters are a class of neurotransmitters. Only three gases are accepted to be classified as gasotransmitters including nitric oxide, carbon monoxide, and hydrogen sulfide.

Gaseous Signaling Molecules

Oxygen

Oxygen, O₂, is an essential gaseous signaling molecule & biological messenger important in many physiological and pathological processes, acting via cellular gasoreceptor proteins and other signaling pathways.^[1][2] The levels of O₂ in cells or organisms must be tighly regulated to ensure normoxic and not uncontrolled hypoxic or anoxic or hyperoxic states. In mammals, specialized tissues such as carotid body sense O₂ levels.

Carbon dioxide

Carbon dioxide, CO₂, is one of the mediators of local

Mosquitoes are attracted to humans by sensing the CO₂ via gustatory receptors, a type of gasoreceptor.^[3]

Although the body requires oxygen for metabolism, low oxygen levels normally do not stimulate breathing. Rather, breathing is stimulated by higher carbon dioxide levels.^[4]

The respiratory centers try to maintain an arterial CO₂ pressure of 40 mm Hg. With intentional hyperventilation, the CO₂ content of arterial blood may be lowered to 10–20 mm Hg (the oxygen content of the blood is little affected), and the respiratory drive is diminished. This is why one can hold one's breath longer after hyperventilating than without hyperventilating. This carries the risk that unconsciousness may result before the need to breathe becomes overwhelming, which is why hyperventilation is particularly dangerous before free diving.

Nitric oxide

Nitric oxide, NO, is a key vertebrate biological messenger important in many physiological and pathological processes, acting, for instance, as a powerful vasodilator in humans (see Biological functions of nitric oxide). Mammalian cells have a specialized gasoreceptor soluble guanylyl cyclase that bind to NO and trigger NO-dependent cellular signaling.

Nitrous oxide

In 1981, it was first suggested from clinical work with nitrous oxide (N₂O) that a gas had a direct action at pharmacological receptors and thereby acted as a neurotransmitter.[9]^[10][11] In vitro experiments confirmed these observations^[12] which were replicated at NIDA later.^[13]

Apart from its direct^[14][15] and indirect actions at opioid receptors,^[16] it was also shown that N₂O inhibits NMDA receptor-mediated activity and ionic currents and diminishes NMDA receptor-mediated excitotoxicity and neurodegeneration.^[17] Nitrous oxide also inhibits methionine synthase and slows the conversion of homocysteine to methionine, increases homocysteine concentration and decreases methionine concentration. This effect was shown in lymphocyte cell cultures^[18] and in human liver biopsy samples.^[19]

Nitrous oxide does not bind as a ligand to the

Endogenous nitrous oxide can possibly play a role in modulating endogenous opioid^[23][24] and NMDA systerosclerosis, severe sepsis, severe malaria, or autoimmunity. Clinical tests involving humans have been performed, but the results have not yet been released.^[25]

Carbon suboxide

Carbon suboxide, C₃O₂, can be produced in small amounts in any biochemical process that normally produces carbon monoxide, CO, for example, during heme oxidation by heme oxygenase-1. It can also be formed from malonic acid. It has been shown that carbon suboxide in an organism can quickly polymerize into macrocyclic polycarbon structures with the common formula (C₃O₂)_n (mostly (C₃O₂)₆ and (C₃O₂)₈), and that those macrocyclic compounds are potent inhibitors of Na⁺/K⁺-ATP-ase and Ca-dependent ATP-ase, and have digoxin-like physiological properties and natriuretic and antihypertensive actions. Those macrocyclic carbon suboxide polymer compounds are thought to be endogenous digoxin-like regulators of Na⁺/K⁺-ATP-ases and Ca-dependent ATP-ases, and endogenous natriuretics and antihypertensives.^[26][27][28] Other than that, some authors think also that those macrocyclic compounds of carbon suboxide can possibly diminish free radical formation and oxidative stress and play a role in endogenous anticancer protective mechanisms, for example in the retina.^[29]

Sulfur dioxide

The role of sulfur dioxide, SO₂, in mammalian biology is not well understood.^[30] Sulfur dioxide blocks nerve signals from the pulmonary stretch receptors and abolishes the Hering–Breuer inflation reflex.

Sulfur dioxide plays a role in diminishing an experimental lung damage caused by oleic acid. Endogenous sulfur dioxide lowered lipid peroxidation, free radical formation, oxidative stress and inflammation during an experimental lung damage. Conversely, a successful lung damage caused a significant lowering of endogenous sulfur dioxide production, and an increase in lipid peroxidation, free radical formation, oxidative stress and inflammation. Moreover, blockade of an enzyme that produces endogenous SO₂ significantly increased the amount of lung tissue damage in the experiment. Conversely, adding acetylcysteine or glutathione to the rat diet increased the amount of endogenous SO₂ produced and decreased the lung damage, the free radical formation, oxidative stress, inflammation and apoptosis.^[31]

Endogenous sulfur dioxide may play a role in regulating

In children with pulmonary arterial hypertension due to congenital heart diseases, the level of homocysteine is higher and the level of endogenous sulfur dioxide is lower than in normal control children. Moreover, these biochemical parameters strongly correlated to the severity of pulmonary arterial hypertension. Authors considered homocysteine to be one of useful biochemical markers of disease severity and sulfur dioxide metabolism to be one of potential therapeutic targets in those patients.^[33]

Endogenous sulfur dioxide also lowers the

Endogenous sulfur dioxide in low concentrations causes endothelium-dependent vasodilation. In higher concentrations it causes endothelium-independent vasodilation and has a negative inotropic effect on cardiac output function, thus effectively lowering blood pressure and myocardial oxygen consumption. The vasodilating effects of sulfur dioxide are mediated via ATP-dependent calcium channels and L-type ("dihydropyridine") calcium channels. Endogenous sulfur dioxide is also a potent antiinflammatory, antioxidant and cytoprotective agent. It lowers blood pressure and slows hypertensive remodeling of blood vessels, especially thickening of their intima. It also regulates lipid metabolism.^[35]

Endogenous sulfur dioxide also diminishes myocardial damage, caused by

Some other researchers have shown that methane, produced by the intestinal flora, is not fully "biologically neutral" to the intestine, and it participates in the normal physiologic regulation of peristalsis. And its excess causes not only belching, flatulence and belly pain, but also functional constipation.^[45]

Ethylene

Ethylene, H₂C=CH₂, serves as a hormone in plants.^[46] It acts at trace levels throughout the life of the plant by stimulating or regulating the ripening of fruit, the opening of flowers, and the abscission (or shedding) of leaves. Commercial ripening rooms use "catalytic generators" to make ethylene gas from a liquid supply of ethanol. Typically, a gassing level of 500 to 2,000 ppm is used, for 24 to 48 hours. Care must be taken to control carbon dioxide levels in ripening rooms when gassing, as high temperature ripening (20 °C; 68 °F) has been seen to produce CO₂ levels of 10% in 24 hours.^[47]

Ethylene has been used since the ancient Egyptians, who would gash figs in order to stimulate ripening (wounding stimulates ethylene production by plant tissues). The ancient Chinese would burn incense in closed rooms to enhance the ripening of pears. In 1864, it was discovered that gas leaks from street lights led to stunting of growth, twisting of plants, and abnormal thickening of stems.^[46] In 1901, a Russian scientist named Dimitry Neljubow showed that the active component was ethylene.^[48] Sarah Doubt discovered that ethylene stimulated abscission in 1917.^[49] It wasn't until 1934 that Gane reported that plants synthesize ethylene.^[50] In 1935, Crocker proposed that ethylene was the plant hormone responsible for fruit ripening as well as senescence of vegetative tissues.^[51]

Ethylene is produced from essentially all parts of higher plants, including leaves, stems, roots, flowers, fruits, tubers, and seeds. Ethylene production is regulated by a variety of developmental and environmental factors. During the life of the plant, ethylene production is induced during certain stages of growth such as germination, ripening of fruits, abscission of leaves, and senescence of flowers. Ethylene production can also be induced by a variety of external aspects such as mechanical wounding, environmental stresses, and certain chemicals including auxin and other regulators.^[52]

Ethylene is

Environmental cues such as flooding, drought, chilling, wounding, and pathogen attack can induce ethylene formation in plants. In flooding, roots suffer from lack of oxygen, or anoxia, which leads to the synthesis of 1-aminocyclopropane-1-carboxylic acid (ACC). ACC is transported upwards in the plant and then oxidized in leaves. The ethylene produced causes nastic movements (epinasty) of the leaves, perhaps helping the plant to lose water.^[54]

Ethylene in plant induces such responses:

• Seedling triple response, thickening and shortening of hypocotyl with pronounced apical hook.
• In pollination, when the pollen reaches the stigma, the precursor of the ethene, ACC, is secreted to the petal, the ACC releases ethylene with ACC oxidase.
• Stimulates leaf and flower senescence
• Stimulates senescence of mature xylem cells in preparation for plant use
• Induces leaf abscission
• Induces seed germination
• Induces root hair growth ^[55]— increasing the efficiency of water and mineral absorption through rhizosheath formation ^[56][57]
• Induces the growth of
  adventitious roots during flooding ^[58][59]
• Stimulates survival under low-oxygen conditions (hypoxia) in submerged plant tissues ^{[60][61][62][63]}
• Stimulates epinasty — leaf petiole grows out, leaf hangs down and curls into itself
• Stimulates
  fruit ripening^[64]
• Induces a climacteric rise in respiration in some fruit which causes a release of additional ethylene.
• Affects gravitropism
• Inhibits root growth in response to soil compaction,^[65][66] shade ^[67][68] and flooding ^[63]
• Stimulates nutational bending
• Inhibits stem growth and stimulates stem and cell broadening and lateral branch growth outside of seedling stage (see Hyponastic response)
• Interference with auxin transport (with high auxin concentrations)
• Inhibits shoot growth and stomatal closing except in some water plants or habitually flooded ones such as some rice varieties, where the opposite occurs (conserving CO
  ₂ and O
  ₂)
• Induces flowering in pineapples
• Inhibits short day induced flower initiation in Pharbitus nil^[69] and Chrysanthemum morifolium^[70]

Small amounts of endogenous ethylene are also produced in