Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptorsOA

The current restrictive criteria for gasotransmitters exclude oxygen(O2)as a gasotrans-mitter in vertebrates.In this manuscript,I propose a revision of gasotransmitter criteria to include O2 per se as a signaling molecule and'essential gasotransmitter'for verte-brates.This revision would enable us to search for protein-based O2-binding sensors(gasoreceptors)in all cells in the brain or other tissues rather than specialized tissues such as the carotid body or gills.If microorganisms have protein-based O2-binding sensors or gasoreceptors such as DosP or FixL or FNR with diverse signaling domains,then eukary-otic cells must also have O2-binding sensors or gasoreceptors.Just as there are protein-based receptor(s)for nitric oxide(GUCY1A,GUCY1B,CLOCK,NR1D2)in cells of diverse tissues,it is reasonable to consider that there are protein-based receptors for O2 in cells of diverse tissues as well.In mammals,O2 must be acting as a gasotransmitter or gaseous signaling molecule via protein-based gasoreceptors such as androglobin that very likely mediate acute sensing of O2.Accepting O2 as an essential gasotransmitter will enable us to search for gasoreceptors not only for O2 but also for other nonessential gasotransmit-ters such as hydrogen sulfide,ammonia,methane,and ethylene.It will also allow us to investigate the role of environment-derived metal ions in acute gas(or solute)sensing within and between organisms.Finally,accepting O2 per se as a signaling molecule acting via gasoreceptors will open up the field of gasocrinology.