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 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 dysfunction in animals with SO2 gas-induced bronchitis by increasing the DSPC-to-protein ratio in the airway.
Kimoto
A
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan. kimoto@yamanouchi.co.jp
Hirano
Y
Y
Iwai
T
T
Saitou
M
M
Tomioka
K
K
Miyata
K
K
Yamada
T
T
D000818:Animals; D001991:Bronchitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects* / Q000502:physiology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D013458:Sulfur Dioxide; D013500:Surface Tension / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D010671:Phenylurea Compounds; D010713:Phosphatidylcholines; D011506:Proteins; D011663:Pulmonary Surfactants; C114914:YM 26818; C017463:lecithins, disaturated; D013458:Sulfur Dioxide