Gaseous mediator

Gaseous mediators are small gaseous molecules that play critical roles in various physiological and pathological processes within the body. Unlike traditional neurotransmitters or hormones, gaseous mediators are not stored in vesicles but are synthesized on demand and can easily diffuse across cell membranes to affect neighboring cells. This article focuses on the three most studied gaseous mediators: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S).

Nitric Oxide (NO)

Nitric oxide is a radical gas and an important cellular signaling molecule involved in many physiological and pathological processes. It is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). NO plays a crucial role in vascular regulation, neurotransmission, and immune responses. It is involved in the regulation of blood pressure, learning and memory, and defense against pathogens. Excessive or insufficient production of NO is associated with various diseases, such as hypertension, neurodegenerative diseases, and septic shock.

Carbon Monoxide (CO)

Carbon monoxide is produced in the body as a byproduct of the degradation of heme by the enzyme heme oxygenase. CO has long been considered merely a toxic gas, but it is now recognized as an important endogenous gaseous mediator. It has anti-inflammatory, anti-apoptotic, and vasodilatory effects. CO is involved in the regulation of blood pressure, prevention of vascular smooth muscle cell proliferation, and protection of tissues from hypoxia-induced damage. However, excessive exposure to CO from external sources can be lethal, as it competes with oxygen for binding to hemoglobin, impairing oxygen delivery to tissues.

Hydrogen Sulfide (H2S)

Hydrogen sulfide is produced in the body from cysteine by the action of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS). H2S was traditionally considered a toxic gas, but it is now recognized as a signaling molecule with important roles in cardiovascular physiology, neurobiology, and cellular stress response. It acts as a vasodilator and modulates inflammatory responses, protects neurons, and regulates apoptosis. Like NO and CO, dysregulation of H2S production or signaling is linked to various diseases, including hypertension, heart failure, and neurodegenerative disorders.

Mechanisms of Action

Gaseous mediators exert their effects through various mechanisms. NO activates the enzyme guanylate cyclase, leading to an increase in cyclic guanosine monophosphate (cGMP) levels, which in turn regulates various cellular functions. CO binds to the heme group of guanylate cyclase, similarly increasing cGMP levels. H2S modulates the activity of various ion channels, including ATP-sensitive potassium channels, and can also sulfhydrate (post-translational modification) specific cysteine residues on target proteins, affecting their function.

Clinical Implications

Understanding the roles of gaseous mediators has led to the development of therapeutic strategies targeting their production or function. For example, nitric oxide donors and phosphodiesterase inhibitors that increase cGMP levels are used to treat conditions such as angina and erectile dysfunction. Research into CO-releasing molecules (CORMs) and H2S donors is ongoing, with the potential for treating cardiovascular diseases, inflammatory conditions, and neurodegenerative diseases.