NO and CO as second messengers in oxygen sensing in the carotid body

Respir Physiol. 1999 Apr 1;115(2):161-8. doi: 10.1016/s0034-5687(99)00019-5.


It is being increasingly appreciated that nitric oxide (NO) and carbon monoxide (CO) are synthesized in mammalian cells and that they function as second messengers. The purpose of this article is to highlight the current information on NO and CO in the carotid body and discuss their significance in oxygen chemoreception. The NO synthesizing enzyme, nitric oxide synthase, is localized to nerve fibers and vascular endothelium in the carotid body. In vitro biochemical assays have shown that acute hypoxia inhibits NO synthase activity in carotid body extracts. Prolonged hypoxia up-regulates mRNA's encoding neuronal and endothelial NO synthases in the carotid body. Physiological studies have shown that NO is inhibitory to the carotid body sensory activity and mediates efferent inhibition. The actions of NO are in part mediated by its effects on glomus cells, wherein NO modulates Ca2+ channel activity and affects [Ca2+]i. The carotid body also uses another highly related gas as a second messenger, carbon monoxide (CO). The enzyme responsible for CO biosynthesis, heme oxygenase-2, is localized to glomus cells. CO, like NO, also exerts an inhibitory influence on sensory activity. Some of the actions of CO are mediated by altering Ca2+ channel activity and [Ca2+]i in glomus cells. Molecular oxygen is essential for biosynthesis of NO and CO. Under normoxia, basal levels of NO and CO act as amplifiers of molecular oxygen and keep the sensory discharge low. During hypoxia, decreased synthesis of NO and CO may contribute in part to the augmentation of sensory discharge.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carbon Monoxide / metabolism*
  • Carotid Body / metabolism*
  • Cell Hypoxia / physiology
  • Chemoreceptor Cells / metabolism
  • Cyclic GMP / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Models, Neurological
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Oxygen / metabolism*
  • Second Messenger Systems
  • Up-Regulation


  • Nitric Oxide
  • Carbon Monoxide
  • Nitric Oxide Synthase
  • Heme Oxygenase (Decyclizing)
  • Cyclic GMP
  • Oxygen