| 11250878 |
Asano T, Hattori T, Tada T, Kajikuri J, Kamiya T, Saitoh M, Yamada Y, Itoh M, Itoh T: Role of the epithelium in opposing H (2) O (2)-induced modulation of acetylcholine-induced contractions in rabbit intrapulmonary bronchiole. Br J Pharmacol. 2001 Mar;132(6):1271-80.
1. The role played by the epithelium in H (2) O (2)-induced modulation of the mechanical responses induced by acetylcholine (ACh) in rabbit intrapulmonary bronchioles was investigated in epithelium-intact and -denuded strips. 2. When ACh (3 microM) was applied intermittently, H (2) O (2) (30 microM) enhanced the ACh-induced contractions in epithelium-intact strips. In contrast, in epithelium-denuded strips H (2) O (2) (30 microM) inhibited such contractions. At higher concentrations, H (2) O (2) concentration-dependently attenuated the ACh-induced contractions in both epithelium-intact and -denuded strips, its action being more potent in the latter strips than in the former. 3. Diclofenac (a cyclo-oxygenase inhibitor; 3 microM) reduced the H (2) O (2)-induced enhancement of ACh-contractions in epithelium-intact strips but had no effect on the H (2) O (2)-induced inhibition in epithelium-denuded strips. N (G)-nitro-L-arginine did not alter the effect of H (2) O (2) on ACh-induced contractions in epithelium-intact strips. 4. Catalase (500 u ml (-1)) completely blocked both H (2) O (2)-induced effects on ACh-contractions (enhancement and inhibition). Neither superoxide dismutase (200 u ml (-1)) nor deferoxamine (0.5 mM) had any effect on H (2) O (2)-induced inhibition in epithelium-denuded strips. 5. Aminotriazole (an inhibitor of catalase; 50 mM) significantly potentiated the H (2) O (2)-induced inhibition of ACh-contractions in epithelium-intact strips but not in epithelium-denuded strips. 6. The density ratio for catalase (epithelium-intact over -denuded strips) analysed by Western blot was about 2.1, suggesting that epithelium contains more catalase than smooth muscle. 7. It is concluded that in rabbit intrapulmonary bronchioles, H (2) O (2) has dual actions on ACh-contractions. It is suggested that the epithelium may act as a powerful biochemical barrier via both the action of catalase (scavenging H (2) O (2)) and the release of bronchoconstrictor prostaglandins, thus attenuating the H (2) O (2)-induced modulation of ACh-contractions. |
3(0,0,0,3) |