| 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
(Affiliation: Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.)
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| Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 356
Issue 4
Pg. 1050-5
(May 18 2007)
ISSN: 0006-291X United States |
| PMID | 17400191
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Bicarbonates
- neltenexine
- Ambroxol
- Chlorine
|
| 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)
|
