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Published on: July 4, 2018
[Effects of theophylline on ion transport in rabbit tracheal epithelium]
K Ichimura1, T Majima, T Horie
1First Department of Internal Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamimachi, Itabashi-ku, Tokyo 173-0032, Japan.
Abstract:
Theophylline has several mechanisms of action, including bronchodilation and anti-inflammatory effects that have found use in the treatment of bronchial asthma. However, theophylline's effects at the cellular level have not been fully elucidated. We examined the influence of theophylline on ion transport in the tracheal epithelium of rabbits. To measure ion transport, we used the voltage clamp method. When theophylline was applied to the submucosal side of tissue specimens, no remarkable change in short circuit current (Isc) was noted: however, Isc increased in a dose-dependent manner when theophylline was administered to the mucosal side. Although pretreatment with a Cl channel blocker (diphenylamine 2-carboxylate) suppressed theophylline-induced increases in Isc, a Na channel blocker (amiloride) and Ca-dependent Cl channel blocker (4,4-diisthiocyanatosilbene-2, 2-disultonic acid) did not alter the Isc response to theophylline. These results suggest that theophylline influences tracheal water flow by stimulating the c-AMP dependent Cl channel and inducing Cl secretion.
Insights
Theophylline stimulates chloride secretion in rabbit tracheal epithelium by activating cAMP-dependent channels on the mucosal side. This finding clarifies theophylline's cellular mechanisms in treating asthma.
Area of Science:
- Respiratory Physiology
- Cellular Biology
- Pharmacology
Context:
- Theophylline is a bronchodilator and anti-inflammatory agent used for asthma.
- Its precise cellular mechanisms, particularly regarding ion transport in the airway epithelium, remain incompletely understood.
Purpose:
- To investigate the effect of theophylline on ion transport in rabbit tracheal epithelium.
- To elucidate the specific ion channels and pathways involved in theophylline's action.
Summary:
- Theophylline applied to the mucosal side of rabbit tracheal epithelium dose-dependently increased short-circuit current (Isc), indicating active ion transport.
- This increase was inhibited by diphenylamine 2-carboxylate, a chloride channel blocker, but not by amiloride (sodium channel blocker) or a calcium-dependent chloride channel blocker.
- These findings suggest theophylline stimulates cAMP-dependent chloride channels, promoting chloride secretion.
Impact:
- Provides a clearer understanding of theophylline's cellular effects on airway epithelium.
- Identifies specific ion channels (cAMP-dependent chloride channels) mediating theophylline's action.
- Contributes to the knowledge base for developing more targeted asthma therapies.
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