Oxygen is an essential gasotransmitter directly sensed via protein gasoreceptors.

The current restrictive criteria for gasotransmitters exclude oxygen (O 2 ) as a gasotransmitter in vertebrates. In this manuscript, I propose a revision of gasotransmitter criteria to include O 2 per se as a signaling molecule and 'essential gasotransmitter' for vertebrates. This revision would enable us to search for protein-based O 2 -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 O 2 -binding sensors or gasoreceptors such as DosP or FixL or FNR with diverse signaling domains, then eukaryotic cells must also have O 2 -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 O 2 in cells of diverse tissues as well. In mammals, O 2 must be acting as a gasotransmitter or gaseous signaling molecule via protein-based gasoreceptors such as androglobin that very likely mediate acute sensing of O 2 . Accepting O 2 as an essential gasotransmitter will enable us to search for gasoreceptors not only for O 2 but also for other nonessential gasotransmitters 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 O 2 per se as a signaling molecule acting via gasoreceptors will open up the field of gasocrinology.