Gasotransmitter

Gasotransmitters are a unique class of endogenous signaling molecules that are gases at physiological temperatures. They are produced on demand and can freely diffuse across cellular membranes without the need for transporters or receptors in the traditional sense. The three most studied gasotransmitters are nitric oxide, carbon monoxide, and hydrogen sulfide. Each of these gases acts as both a neurotransmitter and a vasodilator, modulating processes such as blood pressure regulation, platelet aggregation, and inflammatory responses.

Nitric oxide was the first gasotransmitter to be discovered, with its synthase enzymes (NOS) identified in the 1990s. It activates soluble guanylate cyclase, increasing cyclic GMP levels and inducing smooth muscle relaxation. Carbon monoxide, traditionally viewed as toxic, is generated by heme oxygenase enzymes and signals through soluble guanylate cyclase and other targets such as ion channels. Hydrogen sulfide, produced by cystathionine γ‑lyase and cystathionine β‑synthase, modulates cellular signaling via sulfhydration of proteins and activation of potassium channels.

The signaling pathways of gasotransmitters are distinct because the molecules themselves diffuse directly to target cells and bind to intracellular sites. This makes them highly efficient but also raises challenges for therapeutic manipulation, as their short half‑lives demand precise delivery methods. Recent advances in drug delivery and biosensor technology have renewed interest in harnessing gasotransmitter pathways for treating conditions such as hypertension, neurodegeneration, and cardiovascular disease. Despite this progress, debates continue regarding optimal dosing, off‑target effects, and the broader implications of modulating gas signaling in humans.