Gasotransmitters (NO, CO, CH4, H2S)
Figure 16: gasotransmitters synthesis and their producing enzymes
Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) collectively known as gasotransmitters (Fig.16). These gases were considered to be highly toxic and hazardous to the environment. Under normal physiological conditions in mammals these molecules are enzymatically regulated and endogenously synthesized. They are lipid-soluble, endogenously produced gaseous messenger molecules and have emerged as potent cytoprotective mediators in various models of tissue and cellular injury. At physiological levels, the exogenous and endogenous manipulation of these three gases has been shown to modulate a number of cytoprotective mechanisms including: vasodilatation, inhibition of apoptosis, modulation of mitochondrial respiration, antioxidants, and inhibition of inflammation. Studies have found that deficiencies in the enzymes (through genetic manipulation or use of inhibitors) exacerbate ischemia-reperfusion (I/R) injury, whereas genetic overexpression of the enzymes induces cytoprotection. Furthermore, treatment with pharmacological donors or inhaled gas therapy has also been shown to provide cytoprotection.
However, while their actions are similar, there are some differences in the mechanisms by which these gasotransmitters induce these effects and the regulatory actions of the enzyme systems can vary depending upon the gas being investigated. Furthermore, it does appear to be some crosstalk between the gases, which can provide synergistic and additional regulatory effects.