Signaling by gasotransmitters

Abstract

Nitric oxide is well established as a major signaling molecule. Evidence is accumulating that carbon monoxide and hydrogen sulfide also are physiologic mediators in the cardiovascular, immune, and nervous systems. This Review focuses on mechanisms whereby they signal by binding to metal centers in metalloproteins, such as in guanylyl cyclase, or modifying sulfhydryl groups in protein targets.

Fig. 1

Physiologic vasorelaxation by NO, CO, and H₂S. Stimulation of muscarinic acetylcholine receptors (AChRs) on endothelial cells activates Ca²⁺-calmodulin (CaM), which in turn binds to and stimulates endothelial NO synthase (eNOS), cystathionine γ-lyase (CSE), and HO2 to produce NO, H₂S, and CO, respectively. NO and CO diffuse into the adjacent smooth muscle cells and activate soluble guanylyl cyclase (sGC) to produce cyclic GMP (cGMP), ultimately affecting the actin-myosin cross-bridge. H₂S also diffuses into smooth muscle cells, where it likely activates K⁺ channels. These actions of all three gases lead to vasorelaxation.