H2S mediates O2 sensing in the carotid body.
Gaseousmessengers, nitric oxide and carbon monoxide, have been implicated in O2 sensing by the carotid body, a sensory organ that monitors arterial blood O2 levels and stimulates breathing in response to hypoxia. We now show that hydrogen sulfide (H2S) is a physiologic gasotransmitter of the carotid body, enhancing its sensory response to hypoxia. Glomus cells, the site of O2 sensing in the carotid body, express cystathionine gamma-lyase (CSE), an H2S-generating enzyme, with hypoxia increasing H2S generation in a stimulus-dependent manner. Mice with genetic deletion of CSE display severely impaired carotid body response and ventilatory stimulation to hypoxia, as well as a loss of hypoxia-evoked H2S generation. Pharmacologic inhibition of CSE elicits a similar phenotype in mice and rats. Hypoxia-evoked H2S generation in the carotid body seems to require interaction of CSE with hemeoxygenase-2, which generates carbon monoxide. CSE is also expressed in neonatal adrenal medullary chromaffin cells of rats and mice whose hypoxia-evoked catecholamine secretion is greatly attenuated by CSE inhibitors and in CSE knockout mice.
Peng
Ying-Jie
YJ
Department of Medicine, University of Chicago, IL 60637, USA.
Nanduri
Jayasri
J
Raghuraman
Gayatri
G
Souvannakitti
Dangjai
D
Gadalla
Moataz M
MM
Kumar
Ganesh K
GK
Snyder
Solomon H
SH
Prabhakar
Nanduri R
NR
D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D003542:Cystathionine gamma-Lyase / Q000172:deficiency / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010100:Oxygen / Q000502:physiology*; D051381:Rats
D003542:Cystathionine gamma-Lyase; D010100:Oxygen; D006862:Hydrogen Sulfide