Effects of JTV‐506, a new K<sup>+</sup> channel activator, on airway smooth muscle contraction and systemic blood pressure

1. Lysophosphatidylcholine (Lyso-PC), which is synthesized by phospholipase A2, is generally considered to induce adhesion molecules. However, little is known about the involvement of Lyso-PC in the pathogenesis of bronchial asthma. The present study was designed to examine whether pre-exposure to Lyso-PC causes eosinophil recruitment and an increase in resistance in airways. 2. Eosinophils in bronchoalveolar lavage fluid (BALF) and the airway walls were enumerated after inhalation of 0.5 mg/mL Lyso-PC to guinea-pigs for 10 min. Respiratory resistance (Rrs) was recorded continuously over 6 h after inhalation of an equi-dose of Lyso-PC for an equivalent period. 3. The proportion of eosinophils was increased from 10.7 +/- 3.3 to 27.5 +/- 3.1% (P < 0.0001) in BALF 6 h after inhalation of Lyso-PC, whereas the proportion of neutrophils and lymphocytes was not increased. Histological examination also showed uniform distribution of eosinophils in the airway wall of bronchi and bronchioles 6 h after inhalation of Lyso-PC. The number of eosinophils (/10 h.p.f.) in the bronchi and bronchioles was increased from 43.5 +/- 16.8 to 154.8 +/- 21.7 (P < 0.0001) and from 34.8 +/- 0.7 to 106.0 +/- 26.6 (P < 0.01), respectively. This eosinophil infiltration was similarly observed 24 h later. 4. Next, we examined the effects of eosinophil infiltration induced by Lyso-PC on Rrs. Inhalation of Lyso-PC caused a slow increase in Rrs and the percentage increase in Rrs was 19.8 +/- 1.9% (P < 0.0001) 6 h later. Eosinophil infiltration and an increase in Rrs did not occur after inhalation of physiological saline. These phenomena induced by Lyso-PC were diminished by pretreatment with dexamethasone (6 micro g/kg per day for 3 days). 5. Lysophosphatidylcholine causes eosinophil infiltration and a subsequent increase in resistance in airways. Our results indicate that Lyso-PC may be involved in the pathophysiology of bronchial asthma.

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Effects of JTV‐506, a new K⁺ channel activator, on airway smooth muscle contraction and systemic blood pressure

Cited by 4 publications

References 35 publications

Role of Airway Smooth Muscle in Inflammation Related to Asthma and COPD

Role of Airway Smooth Muscle in Inflammation Related to Asthma and COPD

Potassium channel activators based on the benzopyran substructure: synthesis and activity of the C-8 substituent

Role of Lysophosphatidylcholine in Eosinophil Infiltration and Resistance in Airways

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Effects of JTV‐506, a new K+ channel activator, on airway smooth muscle contraction and systemic blood pressure

Cited by 4 publications

References 35 publications

Role of Airway Smooth Muscle in Inflammation Related to Asthma and COPD

Role of Airway Smooth Muscle in Inflammation Related to Asthma and COPD

Potassium channel activators based on the benzopyran substructure: synthesis and activity of the C-8 substituent

Role of Lysophosphatidylcholine in Eosinophil Infiltration and Resistance in Airways

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Product

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Effects of JTV‐506, a new K⁺ channel activator, on airway smooth muscle contraction and systemic blood pressure