H2S mediates O-2 sensing in the carotid body

作者：Peng Ying Jie; Nanduri Jayasri; Raghuraman Gayatri; Souvannakitti Dangjai; Gadalla Moataz M; Kumar Ganesh K; Snyder Solomon H^*; Prabhakar Nanduri R

来源：Proceedings of the National Academy of Sciences, 2010, 107(23): 10719-10724.

DOI：10.1073/pnas.1005866107

• cystathionine gamma-lyase
• hydrogen sulfide
• hypoxia
• hemeoxygenase-2

Gaseous messengers, nitric oxide and carbon monoxide, have been implicated in O-2 sensing by the carotid body, a sensory organ that monitors arterial blood O-2 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 O-2 sensing in the carotid body, express cystathionine.-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.

• 出版日期2010-6-8