G-Protein-Coupled Receptor (GPCR) Signaling in the Carotid Body: Roles in Hypoxia and Cardiovascular and Respiratory Disease

International Journal of Molecular Sciences

Nikolaos Batis¹  Prem Kumar²  EyasA. Alhuthail²  AndrewM. Coney²  HayyafS. Aldossary²  Demitris Nathanael²  AndrewP. Holmes²  AbdulazizA. Alzahrani²  ClareJ. Ray² 

[1]Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK

[2]Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT, UK

关键词: G-protein;    GPCR;    carotid body;    hypoxia;    hypertension;    drug-discovery;   

DOI  :  10.3390/ijms21176012

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown