The human carotid body releases acetylcholine, ATP and cytokines during hypoxia

Exp Physiol. 2014 Aug;99(8):1089-98. doi: 10.1113/expphysiol.2014.078873. Epub 2014 May 30.

Abstract

Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)-1β, IL-4, IL-6, IL-8 and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia-inducible factor-1α and hypoxia-inducible factor-2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information suggesting that the carotid body may play a role in detecting inflammation, providing a link between the immune system and the nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carotid Body / metabolism*
  • Carotid Body / physiopathology*
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Interleukins / metabolism*
  • Male
  • Middle Aged
  • Neurotransmitter Agents / metabolism
  • Oxygen / metabolism
  • Receptors, Cytokine / metabolism
  • Reflex / physiology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukins
  • Neurotransmitter Agents
  • Receptors, Cytokine
  • endothelial PAS domain-containing protein 1
  • Adenosine Triphosphate
  • Acetylcholine
  • Oxygen