title: Transient receptor potential vanilloid 1 receptors mediate acid-induced mucin secretion via Ca2+ influx in human airway epithelial cells.
abstract: Mucin hypersecretion is a key pathological feature of inflammatory respiratory diseases. Previous studies have reported that acids (gastroesophageal reflux or environmental exposure) induce many respiratory symptoms and are implicated in the pathophysiology of obstructive airway diseases. To understand these mechanisms, we measured acid-induced mucin secretion in human bronchial epithelial cells. In the present study, acid induced inward currents of transient receptor potential vanilloid (TRPV)1 and mucin 5AC (MUC5AC) secretion dose dependently, which were inhibited by TRPV1 antagonist capsazepine in a concentration-dependent manner. TRPV1 agonist capsaicin mediated a concentration-dependent increase in TRPV1 inward currents and MUC5AC secretion. Furthermore, capsaicin enhanced acid-induced TRPV1 inward currents and MUC5AC secretion. Acid-induced Ca(2+) influx was prevented by capsazepine dose dependently and enhanced by capsaicin. Pretreatment only with capsaicin also increased the Ca(2+) concentration in a concentration-dependent manner. These data suggest that pharmacological inhibition of calcium-permeable TRPV1 receptors could be used to prevent acid-induced mucin secretion, thereby providing a potential mechanism to reduce their toxicity.
authors.affiliation: Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People's Republic of China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
mesh_terms: D000402:Airway Obstruction / Q000139:chemically induced / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D019343:Citric Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D055271:Mucin 5AC / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018408:Patch-Clamp Techniques; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D019343:Citric Acid; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium