Serine esterase inhibitor reduces contractions with isolated trachea and lung strips from guinea pigs induced by phospholipase A2.
The regulation of the phospholipid metabolism (arachidonic acid (AA) cascade) plays a key role in the pathogenetic mechanisms of the various forms of bronchial asthma. This pathogenetic mechanism offers also important therapeutic implications. Since AA liberation is modulated by phospholipase A2 (PLP-A2) the authors studied the effects of PLP-A2 on guinea pig airways under in vitro conditions and their responses to action of protease inhibitor. Experiments were performed in organ bath with lung strips and tracheal spirals from male guinea pigs. PLP-A2 caused in both models dose-dependent contractions. Para-aminomethyl-benzoic acid reduced PLP-A2-induced contractions in lung strips and trachea in a similar way. This reduction is apparently due to inhibition of AA liberation. These experimental findings underline the relevance of AA cascade to pathogenesis of bronchoconstriction and bronchial hyperreactivity. They support the clinical effectiveness of para-aminomethylbenzoic acid demonstrated earlier. The search for new potential antiasthmatic drugs with the site of action on AA liberation from phospholipids requires in vitro test systems. Guinea pig airway preparations proved to be a suitable in vitro model. The inhibition of PLP-A2 by protease inhibitors seems to be a principal (corticosteroid-like) way for modulation of bronchoconstriction.
D010129:4-Aminobenzoic Acid / Q000494:pharmacology*; D062365:Aminobenzoates / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000503:physiopathology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology; D062366:para-Aminobenzoates
D062365:Aminobenzoates; D001095:Arachidonic Acids; D062366:para-Aminobenzoates; C015668:4-aminomethylbenzoic acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010129:4-Aminobenzoic Acid