title: Action of neltenexine on anion secretion in human airway epithelia.
abstract: Neltenexine has been applied to human lung diseases such as chronic obstructive pulmonary disease (COPD) as a mucolytic agent. However, we have no information on the neltenexine action in bronchial epithelial cells. We studied the neltenexine action on the ion transport in human submucosal serous Calu-3 cells. Under a hyper-secreting condition caused by terbutaline (a beta2-adrenergic agonist), neltenexine diminished anion secretion by inhibiting the Cl- and HCO3- uptake via Na+/K+/2Cl- cotransporter and Na+/HCO3- cotransporter without blockade of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, and also diminished anion secretion via stimulation of Cl-/HCO3- exchanger, which facilitates the extrusion of more CFTR-permeant anion, Cl-, with the uptake of less CFTR-permeant anion, HCO3-. Thus, neltenexine reduced the hyper-secretion to keep an appropriate fluid level in the airway, providing a possibility that neltenexine can be an effective drug in airway obstructive diseases by decreasing the airway resistance under a hyper-secreting condition.
authors.affiliation: Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Niisato
authors.forename: Isao
authors.initials: I
authors.lastname: Hasegawa
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Tokuda
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Taruno
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Marunaka
mesh_terms: D000551:Ambroxol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001639:Bicarbonates / Q000378:metabolism*; D002460:Cell Line; D002713:Chlorine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D000551:Ambroxol; D002713:Chlorine; C095919:neltenexine