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: Naomi Niisato, Isao Hasegawa, Shinsaku Tokuda, Akiyuki Taruno, Ken-ichi Nakajima, Hiroaki Miyazaki, Yoshinobu Iwasaki, Yoshinori Marunaka
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 356 Issue 4 Pg. 1050-5 (May 18 2007) ISSN: 0006-291X [Print] United States
• PMID: 17400191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bicarbonates
• Ambroxol
• Chlorine
• neltenexine

Topics

• Ambroxol (administration & dosage, analogs & derivatives)
• Bicarbonates (metabolism)
• Cell Line
• Chlorine (metabolism)
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism)
• Humans
• Ion Channel Gating (drug effects, physiology)
• Ion Transport (drug effects, physiology)
• Respiratory Mucosa (drug effects, metabolism)