title: TRPV1 and TRPA1 stimulation induces MUC5B secretion in the human nasal airway in vivo.
abstract: OBJECTIVE
  Nasal transient receptor potential vanilloid 1 (TRPV1) stimulation with capsaicin produces serous and mucinous secretion in the human nasal airway. The primary aim of this study was to examine topical effects of various TRP ion channel agonists on symptoms and secretion of specific mucins: mucin 5 subtype AC (MUC5AC) and B (MUC5B).
  
  
  METHODS
  Healthy individuals were subjected to nasal challenges with TRPV1 agonists (capsaicin, olvanil and anandamide), TRP ankyrin 1 (TRPA1) agonists (cinnamaldehyde and mustard oil) and a TRP melastatin 8 (TRPM8) agonist (menthol). Symptoms were monitored, and nasal lavages were analysed for MUC5AC and MUC5B, i.e. specific mucins associated with airway diseases. In separate groups of healthy subjects, nasal biopsies and brush samples were analysed for TRPV1 and MUC5B, using immunohistochemistry and RT-qPCR. Finally, calcium responses and ciliary beat frequency were measured on isolated ciliated epithelial cells.
  
  
  RESULTS
  All TRP agonists induced nasal pain or smart. Capsaicin, olvanil and mustard oil also produced rhinorrhea. Lavage fluids obtained after challenge with capsaicin and mustard oil indicated increased levels of MUC5B, whereas MUC5AC was unaffected. MUC5B and TRPV1 immunoreactivities were primarily localized to submucosal glands and peptidergic nerve fibres, respectively. Although trpv1 transcripts were detected in nasal brush samples, functional responses to capsaicin could not be induced in isolated ciliated epithelial cells.
  
  
  CONCLUSIONS
  Agonists of TRPV1 and TRPA1 induced MUC5B release in the human nasal airways in vivo. These findings may be of relevance with regard to the regulation of mucin production under physiological and pathophysiological conditions.
authors: Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University.
authors: Lisa
authors: L
authors: Alenmyr
authors: Annkatrin
authors: A
authors: Herrmann
authors: Edward D
authors: ED
authors: Högestätt
authors: Lennart
authors: L
authors: Greiff
authors: Peter M
authors: PM
authors: Zygmunt
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives; D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000008:administration & dosage; D001706:Biopsy; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002923:Cilia / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D063388:Endocannabinoids; D006801:Humans; D007150:Immunohistochemistry; D000432:Methanol / Q000008:administration & dosage; D008875:Middle Aged; D009068:Movement; D055271:Mucin 5AC / Q000378:metabolism; D055257:Mucin-5B / Q000235:genetics / Q000378:metabolism*; D009149:Mustard Plant; D055556:Nasal Lavage; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000378:metabolism; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement; D010938:Plant Oils / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018689:Sensory System Agents / Q000008:administration & dosage* / Q000009:adverse effects; D013548:Sweden; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000819:agonists / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000378:metabolism; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; D015220:Calcium Channels; D063388:Endocannabinoids; C524678:MUC5AC protein, human; C524578:MUC5B protein, human; D055271:Mucin 5AC; D055257:Mucin-5B; D009419:Nerve Tissue Proteins; D010938:Plant Oils; D053284:Polyunsaturated Alkamides; D018689:Sensory System Agents; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; C054256:olvanil; D000171:Acrolein; D002211:Capsaicin; C012843:cinnamaldehyde; D002118:Calcium; C027793:mustard oil; C078814:anandamide; D000432:Methanol