G-protein-coupled receptor (GPCR) signaling in the carotid body: roles in hypoxia and cardiovascular and respiratory disease

Hayyaf S. Aldossary, Abdulaziz A. Alzahrani, Demitris Nathanael, Eyas A. Alhuthail, Clare J. Ray, Nikolaos Batis, Prem Kumar, Andrew M. Coney, Andrew P. Holmes*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)
200 Downloads (Pure)

Abstract

The carotid body (CB) is an important organ located at the carotid bifurcation that constantly monitors the blood supplying the brain. During hypoxia, the CB immediately triggers an alarm in the form of nerve impulses sent to the brain. This activates protective reflexes including hyperventilation, tachycardia and vasoconstriction, to ensure blood and oxygen delivery to the brain and vital organs. However, in certain conditions, including obstructive sleep apnea, heart failure and essential/spontaneous hypertension, the CB becomes hyperactive, promoting neurogenic hypertension and arrhythmia. G-protein-coupled receptors (GPCRs) are very highly expressed in the CB and have key roles in mediating baseline CB activity and hypoxic sensitivity. Here, we provide a brief overview of the numerous GPCRs that are expressed in the CB, their mechanism of action and downstream effects. Furthermore, we will address how these GPCRs and signaling pathways may contribute to CB hyperactivity and cardiovascular and respiratory disease. GPCRs are a major target for drug discovery development. This information highlights specific GPCRs that could be targeted by novel or existing drugs to enable more personalized treatment of CB-mediated cardiovascular and respiratory disease.

Original languageEnglish
Article number6012
Number of pages20
JournalInternational Journal of Molecular Sciences
Volume21
Issue number17
Early online date20 Aug 2020
DOIs
Publication statusPublished - 1 Sept 2020

Keywords

  • Carotid body
  • Drug-discovery
  • G-protein
  • GPCR
  • Hypertension
  • Hypoxia

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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