YM-40461 Improves Airway Clearance in Guinea Pigs with Induced Subacute Bronchitis

The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blu...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2000/12/01, Vol.23(12), pp.1441-1444
Main Authors: KIMOTO, Aishi, HIRANO, Yasuno, IWAI, Takaya, SAITOU, Munetoshi, TOMIOKA, Kenichi, MIYATA, Keiji, YAMADA, Toshimitsu
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
bronchitis
Bronchitis - chemically induced
Bronchitis - drug therapy
Bronchitis - physiopathology
Chronic Disease
Dose-Response Relationship, Drug
Guinea Pigs
Male
Medical sciences
Mucociliary Clearance - drug effects
Mucociliary Clearance - physiology
mucociliary transport
Pharmacology. Drug treatments
Phenylurea Compounds - pharmacology
Phosphatidylcholines - metabolism
Proteins - metabolism
Pulmonary Surfactants - metabolism
Respiratory system
Secretory Rate - drug effects
Sulfur Dioxide
Surface Tension - drug effects
surfactant
Trachea - drug effects
Trachea - metabolism
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Summary:The effects of the surfactant secretagogue YM-40461 on the mucociliary transport (MCT) velocity were examined in guinea pigs with induced bronchitis. Guinea pigs were exposed to SO2 gas (900 ppm, 3 h/d) for 5 d. MCT velocity was measured by the movement of a 30% gelatin solution containing Evans blue dye placed on the tracheal mucosal surface. Repeated doses of YM-40461 improved the MCT guinea pigs with bronchitis within 5 d after the completion of SO2 exposure, with an ED50 value of 3.1 mg/kg p.o. At a dose of 10 mg/kg p.o., YM-40461 restored MCT to the control level (98.0% recovery). Ambroxol, bromhexine and salbutamol also improved MCT, but were far less effective than YM-40461. Airway fluid collected from bronchitic animals revealed increased disaturated phosphatidylcholine (DSPC, a major component of surfactants)-to-protein ratio and decreased surface tension produced by YM-40461 treatment (10 mg/kg). These results suggest that YM-40461 ameliorates MCT dysfuction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.23.1441