Expression of taste receptors in Solitary Chemosensory Cells of rodent airways (original) (raw)
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Chemosensors in the Nose: Guardians of the Airways
Physiology, 2013
The G-protein-coupled receptor molecules and downstream effectors that are used by taste buds to detect sweet, bitter, and savory tastes are also utilized by chemoresponsive cells of the airways to detect irritants. Here, we describe the different cell types in the airways that utilize taste-receptor signaling to trigger protective epithelial and neural responses to potentially dangerous toxins and bacterial infection.
Nasal Solitary Chemoreceptor Cell Responses to Bitter and Trigeminal Stimulants In Vitro
Journal of Neurophysiology, 2008
Nasal trigeminal chemosensitivity in mice and rats is mediated in part by epithelial solitary chemoreceptor (chemosensory) cells (SCCs), but the exact role of these cells in chemoreception is unclear (Finger et al. 2003). Histological evidence suggests that SCCs express elements of the bitter taste transduction pathway including T2R (bitter taste) receptors, the G protein8 9-gustducin, PLC<2, and TRPM5, leading to speculation that SCCs are the receptor cells that mediate trigeminal nerve responses to bitter taste receptor ligands. To test this hypothesis, we used calcium imaging to determine whether SCCs respond to classic bitter-tasting or trigeminal stimulants.
PLOS ONE, 2018
The nasal cavity hosts an array of chemoresponsive cells, including the extended olfactory system and several other cells involved in detection of and responses to irritants. Solitary chemosensory cells (SCCs), which respond to irritants and bacteria, express the transient receptor potential channel TRPM5 an essential element of the taste transduction-signaling cascade. Microvillous cells (MVCs), non-neuronal cells situated in the apical layer of the main olfactory epithelium, also express TRPM5, but their function has not yet been clarified. TRPM5-positive MVCs, like SCCs, show a cholinergic phenotype expressing choline acetyl transferase (ChAT), but none of the other elements of the bitter taste transduction cascade could be detected. We reexamined TRPM5-positive MVCs with more sensitive gene expression and staining techniques to clarify whether they rely only on TRPM5 and ChAT or express other elements of the taste/SCC transduction cascade. Analyzing existing RNA sequencing data from whole olfactory mucosa and isolated olfactory sensory neurons, we determined that several elements of the taste/SCC transduction cascade, including taste receptors, are expressed in the olfactory mucosa in cells other than olfactory sensory neurons. Immunostaining confirmed the presence TRPM5 and ChAT in a subset of cells of the olfactory mucosa, which also showed the expression of PLCB2, gustducin, and T1R3. Specifically, these cells were identified as TRPM5-positive MVCs. Furthermore, we examined whether MVCs are innervated by trigeminal fibers, similarly to SCCs. Using antibodies against trigeminal nerve markers calcitonin gene-related peptide and substance P, we determined that, despite the cholinergic phenotype, most MVCs in the olfactory mucosa lacked consistent trigeminal innervation. Our findings indicate that MVCs, like SCCs, express all the elements of the bitter taste transduction cascade but that, unlike SCCs, they possess only sparse trigeminal innervation. The cholinergic phenotype of MVCs suggests a modulatory function of the surrounding olfactory epithelium, through the release of acetylcholine.
Life Sciences, 2010
Aims: The ability to sense the bitter taste of nicotine is an important component of addiction to, and withdrawal from, cigarette smoking. α-Gustducin and phospholipase C-β2 (PLC-β2), molecules involved in the taste transduction pathway, have been identified in airway epithelial solitary chemosensory cells (SCCs). Airway epithelial cells also express multiple nicotinic acetylcholine receptors (nAChRs). However, the relationship between nAChRs and molecules of taste transduction in response to nicotine is not known. This study was designed to determine whether nAChRs and the taste transduction molecules α-gustducin, PLC-β2 and bitter taste receptors (T2R38) reside at sites of the intrapulmonary airways where interaction with the nicotine components of cigarette smoke is likely. Main methods: We used the reverse transcription-polymerase chain reaction (RT-PCR) to detect α-gustducin, PLC-β2 and T2R38 mRNA and immunohistochemistry to localize expression of these proteins by nAChR expressing cells of the airway. Key findings: RT-PCR demonstrated the presence of mRNA for α-gustducin, PLC-β2 and T2R38. Immunohistochemistry showed the expression of α-gustducin, PLC-β2 and T2R38 by subsets of epithelial cells at all levels of the intrapulmonary airways including bronchi, terminal and respiratory bronchioles. Double labeling demonstrated the co-expression of α-gustducin with α3, α4, α5, α7 and β2, as well as, PLC-β2 and T2R38 with α4, α5 and β2 nAChR subunits. Significance: These findings provide morphological evidence for the presence of molecules of the bitter taste transduction pathway in nAChR expressing SCCs of the intrapulmonary airways. These SCCs may, thus, constitute a peripheral component of the bitter taste signal transduction pathway for nicotine.
The taste cell-related diffuse chemosensory system
Progress in Neurobiology, 2005
Elements expressing the molecular mechanisms of gustatory transduction have been described in several organs in the digestive and respiratory apparatuses. These taste cell-related elements are isolated cells, which are not grouped in buds, and they have been interpreted as chemoreceptors. Their presence in epithelia of endodermal origin suggests the existence of a diffuse chemosensory system (DCS) sharing common signaling mechanisms with the ''classic'' taste organs. The elements of this taste cell-related DCS display a site-related morphologic polymorphism, and in the past they have been indicated with various names (e.g., brush, tuft, caveolated, fibrillo-vesicular or solitary chemosensory cells). It may be that the taste cell-related DCS is like an iceberg: the taste buds are probably only the most visible portion, with most of the iceberg more caudally located in the form of solitary chemosensory cells or chemosensory clusters. Comparative anatomical studies in lower vertebrates suggest that this 'submerged' portion may represent the most phylogenetically ancient component of the system, which is probably involved in defensive or digestive mechanisms. In the taste buds, the presence of several cell subtypes and of a wide range of molecular mechanisms permits precise food analysis. The larger, 'submerged' portion of the iceberg is composed of a polymorphic population of isolated elements or cell clusters in which the molecular cascade of cell signaling needs to be explored in detail. The little data we have strongly suggests a close relationship with taste cells. Morphological and biochemical considerations suggest that the DCS is a potential new drug target. Modulation of the respiratory and digestive apparatuses through substances, which act on the molecular receptors of this chemoreceptive system, could be a new frontier in drug discovery. #
Solitary chemoreceptor cell proliferation in adult nasal epithelium
Journal of Neurocytology, 2005
Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium . Many nasal SCCs express the G-protein α-gustducin as well as other elements of the bitter-taste signaling cascade including phospholipase Cβ2, TRPM5 and T2R bitter-taste receptors. While some populations of sensory cells are replaced throughout life (taste and olfaction), others are not (hair cells and carotid body chemoreceptors). These experiments were designed to test whether new SCCs are generated within the epithelium of adult mice. Wild type C57/B6 mice were injected with the thymidine analog 5-bromo-2'deoxyuridine (BrdU) to label dividing cells. At various times after injection (1-40 days), the mice were perfused with 4% paraformaldehyde and prepared for dual-label immunocytochemistry. Double labeled cells were detected as early as 3 days post BrdU injection and remained for as long as 12 days post-injection suggesting that SCCs do undergo turnover like the surrounding nasal epithelium. No BrdU labeled cells were detected after 24 days suggesting relatively rapid replacement of the SCCs.
Taste Receptors in Upper Airway Innate Immunity
Nutrients
Taste receptors, first identified on the tongue, are best known for their role in guiding our dietary preferences. The expression of taste receptors for umami, sweet, and bitter have been demonstrated in tissues outside of the oral cavity, including in the airway, brain, gastrointestinal tract, and reproductive organs. The extra-oral taste receptor chemosensory pathways and the endogenous taste receptor ligands are generally unknown, but there is increasing data suggesting that taste receptors are involved in regulating some aspects of innate immunity, and may potentially control the composition of the nasal microbiome in healthy individuals or patients with upper respiratory diseases like chronic rhinosinusitis (CRS). For this reason, taste receptors may serve as potential therapeutic targets, providing alternatives to conventional antibiotics. This review focuses on the physiology of sweet (T1R) and bitter (T2R) taste receptors in the airway and their activation by secreted bacter...
Olfactory Receptors in Human Airway Epithelia
Methods in Molecular Biology, 2013
Olfactory receptors (OR) represent one of the largest gene families in the human genome. In spite of a signi fi cant progress in deciphering the physiological functions of olfactory receptors, how the majority of these G-protein-coupled receptors are activated is still mostly a mystery. Consequently, for the majority of OR genes there are currently no assigned physiological or behavioral functions. Deciphering ligand speci fi cities and physiological signi fi cance of human ORs is important for understanding how the human olfactory genome encodes odors, and how such odors drive human behavior in health and disease. Although OR genes were originally thought to be restricted to the olfactory epithelium, several recent studies indicated that some members of the OR family might be acting outside the canonical chemosensory system. In a recent study, we have shown that the human airway epithelial cells can also act as chemosensory cells by directly sensing the inhalation of noxious bitter compounds, which can lead to increased mucociliary clearance, and hence may serve as a protective mechanism against inhaled toxins and microorganisms. Whether the airway epithelium can detect chemicals via other sensory pathways has not been reported to date. As a step in this direction, we describe methods for studying the cellular and subcellular localization of olfactory receptor proteins and mRNAs in human airways in both primary in vitro cultures and tissue sections.