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- Title
TRPM8, ASIC1, and ASIC3 localization and expression in the human oropharynx.
- Authors
Alvarez‐Berdugo, D.; Rofes, L.; Casamitjana, J. F.; Enrique, A.; Chamizo, J.; Viña, C.; Pollán, C. M.; Clavé, P.
- Abstract
Background: Oropharyngeal dysphagia (OD) is a prevalent disease with poor prognosis among older people and has no pharmacological treatment. Polymodal sensory receptors like the TRP or ASIC family receptors are potential targets to treat OD. TRPM8 agonists and acidic solutions can improve the swallow response in patients with OD, but little is known about the expression of TRPM8, ASIC1, and ASIC3 in the human oropharynx. The aim of this study was to assess the expression and localization of TRPM8, ASIC1, and ASIC3 in human samples of the oropharynx to lay the basis for new pharmacological treatments for OD. Methods: Pathology‐free samples from oropharyngeal regions innervated by cranial nerves V, IX, and X were obtained during major ENT surgery and processed to obtain mRNA (20 patients) or to be used in immunohistochemical assays (12 patients). TRPM8, ASIC1, and ASIC3 expression and localization were studied with RT‐qPCR and fluorescent immunohistochemistry. Key Results: ASIC3 was expressed in the 3 regions studied with similar levels and was localized on sensory fibers innervating the mucosa below the basal lamina of all studied regions. TRPM8 was also co‐localized on the sensory fibers innervating the mucosa below the basal lamina of all studied regions. In contrast, ASIC1 was only found in the nerves innervating the tongue muscular fibers. Conclusions & Inferences: TRPM8 and ASIC3 are found on submucosal sensory nerves in the human oropharynx. Our study lays the basis to use oropharyngeal TRPM8 and ASIC3 receptors as therapeutic targets to develop new active pharmacological treatments for OD patients. Previous studies have proved the therapeutic effect of TRPM8 and ASIC agonists on neurogenic OD patients, but little is known about the expression and localization of these receptors in the oropharynx.This study explores the expression and localization of TRPM8, ASIC1, and ASIC3 in human oropharyngeal samples with RT‐qPCR and fluorescent immunohistochemistry.ASIC3 expression is found throughout the oropharynx. TRPM8 and ASIC3 are immunolocalized on the sensory nerves innervating the oropharyngeal mucosa. ASIC1 is only found on sensory nerves innervating the tongue muscles.Oropharyngeal TRPM8 and ASIC receptors are promising therapeutic targets to develop active treatments for OD patients.
- Subjects
OROPHARYNX; PHARYNGEAL diseases; CRANIAL nerves; IMMUNOHISTOCHEMISTRY; MUCOUS membranes; ACID-sensing ion channels; PROTEIN expression
- Publication
Neurogastroenterology & Motility, 2018, Vol 30, Issue 11, pN.PAG
- ISSN
1350-1925
- Publication type
Article
- DOI
10.1111/nmo.13398