Inhaled lysophosphatidylcholine provokes bronchoconstriction in guinea pigs in vivo.
Lysophosphatidylcholine is increased in the airway of bronchial asthma, but its role is not clear. We investigated the role of lysophosphatidylcholine in asthma in anaesthetized, mechanically ventilated guinea pigs. Pressure at the airway opening was measured as an index of bronchial response. Increasing doses of lysophosphatidylcholine (1--10 mg/ml) were inhaled and then bronchoalveolar lavage was carried out. 100 and 200 microg/ml methacholine were inhaled 10 min after inhalation of 2.5 mg/ml lysophosphatidylcholine, 10 mg/ml dipalmitoyl phosphatidylcholine and 10 mg/ml glycerophosphocholine, all of which per se did not change the pressure at the airway opening. Effect of 1.0 microg/kg salbutamol, or 60 mg/kg diphenhydramine on the lysophosphatidylcholine-induced increase in the pressure at the airway opening was investigated. Inhalation of lysophosphatidylcholine dose-dependently increased the pressure at the airway opening and increased bronchial responsiveness to methacholine. On the other hand, inhalation of dipalmitoyl phosphatidylcholine decreased the pressure at the airway opening and decreased bronchial responsiveness to methacholine. Intravenously administered salbutamol, but not diphenhydramine, prevented the lysophosphatidylcholine-induced increase in the pressure at the airway opening. The percentage of leukocytes in bronchoalveolar lavage fluid did not change significantly at least within 20 min after the lysophosphatidylcholine inhalation. Lysophosphatidylcholine causes bronchoconstriction and enhances bronchial responsiveness without inducing leukocyte infiltration in the airway, suggesting that lysophosphatidylcholine may be a new bronchoconstrictor mediator in bronchial asthma.
Nobata
Kouichi
K
Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Japan. k-nobata@yg7.so-net.ne.jp
Kurashima
Kazuyoshi
K
Fujimura
Masaki
M
Abo
Miki
M
Ishiura
Yoshihisa
Y
Kasahara
Kazuo
K
Nakao
Shinji
S
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000420:Albuterol; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000503:physiopathology*; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001993:Bronchodilator Agents; D006168:Guinea Pigs; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D008244:Lysophosphatidylcholines; D016210:Methacholine Chloride; D015060:1,2-Dipalmitoylphosphatidylcholine; D000420:Albuterol