Yağ Asidi Amid Hidrolaz (Faah) ve Monoaçil Gliserol Lipaz (Magl) İnhibitörlerinin Farede Deneysel Solunum Yolu İnflamasyonu Üzerindeki Etkileri

Abstract

The endocannabinoid system is a modulator of physiological functions in various biological systems including the airways. In the present study the effects of treatment with the inhibitors of endocannabinoid-degrading enzymes FAAH and MAGL were examined in experimental airway inflammation and tracheal hyperreactivity in mice. Airway inflammation was induced by intranasal (i.n.) lipopolysaccharide (LPS) (60 μl;0,1 mg/ml) application to mice. FAAH inhibitor URB597 [0.3 mg/kg (i.n./i.p.)] and MAGL inhibitor JZL184 [1 mg/kg (i.n.)/5 mg/kg (i.p.)] treatments were given to subgroups one hour before LPS application. Fourty-eight hours after LPS/vehicle application, tracheas and lungs were isolated. LPS application lead to an increase in 5-hydroxytryptamine (5-HT) contractions in isolated tracheal rings while carbachol contractions remained unchanged. The increased 5-HT contractions were prevented by both URB597 and JZL184 treatments. I.p. treatment with URB597 and JZL184, and i.n. treatment with JZL184 reduced peribronchial and parenchymal inflammation in LPS group. However only i.p. URB597 treatment prevented the increase in neutrophil count. These results indicate that FAAH and MAGL inhibition may have a protective effect in airway inflammation and airway hyperreactivity. However, due to the variable effects of these inhibitors on inflammation, the therapeutic value of FAAH and MAGL inhibitors on chronic inflammatory airway diseases should be further investigated.