Role of Ectopic Olfactory Receptors in the Regulation of the Cardiovascular–Kidney–Metabolic Axis

Beito, Mitchell R.; Ashraf, Sadia; Odogwu, Dorcas; Harmancey, Romain

doi:10.3390/life14050548

Life

2024

DOI: 10.3390/life14050548

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Role of Ectopic Olfactory Receptors in the Regulation of the Cardiovascular–Kidney–Metabolic Axis

Mitchell R. Beito,

Sadia Ashraf,

Dorcas Odogwu

et al.

Abstract: Olfactory receptors (ORs) represent one of the largest yet least investigated families of G protein-coupled receptors in mammals. While initially believed to be functionally restricted to the detection and integration of odors at the olfactory epithelium, accumulating evidence points to a critical role for ectopically expressed ORs in the regulation of cellular homeostasis in extranasal tissues. This review aims to summarize the current state of knowledge on the expression and physiological functions of ectopi… Show more

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2024

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Cited by 2 publications

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Functional characterization of OR51B5 and OR1G1 in human lung epithelial cells as potential drug targets for non-type 2 lung diseases

Awad,

Weidinger,

Greune

et al. 2024

Cell Biol Toxicol

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Background Hypersensitivity to odorants like perfumes can induce or promote asthma with non-type 2 inflammation for which therapeutic options are limited. Cell death of primary bronchial epithelial cells (PBECs) and the release of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8 are key in the pathogenesis. Extra-nasal olfactory receptors (ORs) can influence cellular processes involved in asthma. This study investigated the utility of ORs in epithelial cells as potential drug targets in this context. Methods We used the A549 cell line and primary bronchial epithelial cells using air–liquid interface culture system (ALI-PBECs). OR expression was investigated by RT-PCR, Western blot, and Immunofluorescence. Effects of OR activation by specific ligands on intracellular calcium concentration, cAMP, Phospholipase C (PLC), cell viability, and IL-6 and IL-8 secretion were analyzed by calcium imaging, enzyme immunoassays, Annexin V/ propidium iodide -based fluorescence-activated cell staining or by ELISA, respectively. Results By screening A549 cells, the OR51B5 agonists Farnesol and Isononyl Alcohol and the OR1G1 agonist Nonanal increased intracellular Ca2 + . OR51B5 and OR1G1 mRNAs and proteins were detected. Both receptors showed a preferential intracellular localization. OR51B5- but not OR1G1-induced Ca2 + dependent on both cAMP and PLC signaling. Farnesol, Isononyl Alcohol, and Nonanal, all reduced cell viability and induced IL-8 and IL-6 release. The data were verified in ALI-PBECs. Conclusion ORs in the lung epithelium might be involved in airway-sensitivity to odorants. Their antagonism could represent a promising strategy in treatment of odorant-induced asthma with non-type 2 inflammation. Graphical Abstract

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Functional characterization of OR51B5 and OR1G1 in human lung epithelial cells as potential drug targets for non-type 2 lung diseases

Awad,

Weidinger,

Greune

et al. 2024

Cell Biol Toxicol

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Olfactory Receptors and Aortic Aneurysm: Review of Disease Pathways

Stougiannou,

Christodoulou,

Karangelis

2024

JCM

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Aortic aneurysm, the pathological dilatation of the aorta at distinct locations, can be attributed to many different genetic and environmental factors. The resulting pathobiological disturbances generate a complex interplay of processes affecting cells and extracellular molecules of the tunica interna, media and externa. In short, aortic aneurysm can affect processes involving the extracellular matrix, lipid trafficking/atherosclerosis, vascular smooth muscle cells, inflammation, platelets and intraluminal thrombus formation, as well as various endothelial functions. Many of these processes are interconnected, potentiating one another. Newer discoveries, including the involvement of odorant olfactory receptors in these processes, have further shed light on disease initiation and pathology. Olfactory receptors are a varied group of G protein coupled-receptors responsible for the recognition of chemosensory information. Although they comprise many different subgroups, some of which are not well-characterized or identified in humans, odorant olfactory receptors, in particular, are most commonly associated with recognition of olfactory information. They can also be ectopically localized and thus carry out additional functions relevant to the tissue in which they are identified. It is thus the purpose of this narrative review to summarize and present pathobiological processes relevant to the initiation and propagation of aortic aneurysm, while also incorporating evidence associating these ectopically functioning odorant olfactory receptors with the overall pathology.

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Role of Ectopic Olfactory Receptors in the Regulation of the Cardiovascular–Kidney–Metabolic Axis

Cited by 2 publications

References 153 publications

Functional characterization of OR51B5 and OR1G1 in human lung epithelial cells as potential drug targets for non-type 2 lung diseases

Functional characterization of OR51B5 and OR1G1 in human lung epithelial cells as potential drug targets for non-type 2 lung diseases

Olfactory Receptors and Aortic Aneurysm: Review of Disease Pathways

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