PMC:5903065 / 2254-7757
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5903065","sourcedb":"PMC","sourceid":"5903065","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5903065","text":"Olfactory Receptors in the Brain and Heart-Related Systems\nSince the expression of ORs in mammalian germ cells was reported [7], OR expression in various organs and tissues in animals has been observed. The brain and the heart are the fundamental organs that form the basis of animal life. For example, controlling the fluctuation of blood pressure and pulse of an animal is accomplished by endocrine action through autonomic reflex and peptide hormone secretion. Brain and heart are closely connected to each other by various mechanisms, including the nervous system.\nFor the first time, prostate-specific G protein-coupled receptors (PSGRs), also known as RA1c, were reported to be expressed in the brain of rat [13] and mouse [14] and the heart of rat and mouse [15]. It was not expected to be expressed in human tissues other than prostate.\n\nBrain\nAfter it was demonstrated that RA1c homologs—Olr59 in rat [13] and Olfr78 in mouse [14]—were expressed in areas of the brain and olfactory epithelium, much effort has been made to confirm the expression of ORs in the brain. MOL2.3, called Olfr78, was reported to be expressed in the ganglia of the autonomic nervous system [16]. Some mouse ORs—M71 (olfr151), C6 (Olfr49), and OR3—are detected in the cerebral cortex and might play a role in developmental processes, such as axon guidance and target recognition during the postnatal period [17]. OR expression (OR1E1, OR2J3, OR2L13, OR11H1, and OR52L1) in the frontal cortex is downregulated in Parkinson disease (PD) patients [18].\nThe expression of a mouse OR, Olfr110, was detected in the cerebral cortex of wild-type mice for 1 postnatal year, and its mRNA levels did not vary during that period [19]. It was observed that 8 ORs and 6 taste receptors (TASRs) are constitutively expressed in the frontal cortex, entorhinal cortex, and cerebellum in human control brains. These data imply that variable dysregulation of certain ORs and TASRs is common in several neurodegenerative diseases, including Alzheimer disease, Progressive Supranuclear Palsy, and Creutzfeldt–Jakob disease. The same research group also reported a decrease in olfactory and TASR expression in the dorsolateral prefrontal cortex in chronic schizophrenia [20]. There was a report that ORs are expressed in mouse mesencephalic dopaminergic (mDA) neurons. After screening ligands on Olfr287, carvone enantiomers were identified as agonists of Olfr287 and able to increase intracellular Ca2＋ in solitary mDA neurons. The ORs were found to be expressed in human Substantia Nigra and downregulated in PD postmortem brains [21].\nGong et al. [22] found that some ORs are differentially expressed in the sciatic nerve and dorsal root ganglia after sciatic nerve injury in rats. The expression and expression profile of several ORs in the sciatic nerve were verified, and they also observed that the expression of some ORs in primary cultures of Schwann cells was upregulated under H2O2 stimulation [22]. Recently, there has been a report that Olfr544 is expressed in mouse brain and heart, as well as nose, adipose tissue, and spleen [23].\n\nHeart-related system\nIn 1995, Drutel et al. [9] reported the expression of OL1 (Olr1654) in the developing rat heart and suggested its involvement in cardiac morphogenesis, where the OR was hardly detectable at the adult stages. As mentioned above, murine PSGRs (Olfr78 and Olr59) are expressed in the hearts of mouse [16] and rat [15], in addition to prostate. In 2007, Zhang et al. [24] reported that ORs (including OR10G4) are expressed in human heart and various organs using reverse transcription–polymerase chain reaction (RTPCR) and microarray.\nRecently, OR10J5 was found to be expressed in human aorta, coronary artery, and human umbilical vein endothelial cells [25]. In addition, Matrigel plug assay showed that lyral enhances angiogenesis in vivo. These results let us surmise the physiological role of OR10J5 in angiogenesis.\nChang et al. [26] showed that a short-chain fatty acid OR, Olfr78, is highly and selectively expressed in oxygensensitive glomus cells of the carotid body (CB). The CB is a chemosensory organ that monitors blood oxygen to control breath [27]. As lactate eventually activates Olfr78 in heterologous expression experiments, Chang et al. [26] proposed that Olfr78 may act as a hypoxia sensor in the breathing circuit, in addition to its role in olfaction. The next year, Zhou et al. [28] applied the single-cell RNA-Seq method to eliminate the contamination of genes derived from other cell types present in the CB to analyze the expression of ORs in CB glomus cells and identified Olfr78 as the most highly abundant OR in the CB in mice. More recently, Jovancevic et al. [29] reported that OR51E1 activation by the application of cognate agonists induces a negative chronotropic effect in human stem cell-derived cardiomyocytes and also provokes negative inotropic activity in cardiac trabeculae and slice preparations of human explated ventricles. These results imply that some ORs that are expressed in heart may be therapeutic targets for the metabolic regulation of cardiac function. A mouse OR—Olfr544, an ortholog of the OR52 family (OR52K1)—was reported to be expressed in the heart of mice [23]. The unexpected cardiac expression of ORs may regulate cell growth and morphogenesis.\nGeneral studies on OR expression show that ORs are expressed throughout systems and have diverse functions throughout the body of animals (Table 1) [7-11, 13-26, 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