Yu Ye, Wang Xiang, Cui Yun, Fan Ying-Zhe, Liu Jing, Wang Rui
Department of Biochemistry and Molecular Biology, School of Life Science, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Peptides. 2006 Nov;27(11):2770-7. doi: 10.1016/j.peptides.2006.06.002. Epub 2006 Aug 9.
To assess whether diabetes alters the regulatory effects of mu-opioid receptor (MOR) agonists on the cholinergic bronchoconstriction, we investigated the inhibitory effects of endomorphins (EMs) on the electrical field stimulation (EFS)-induced cholinergic bronchoconstriction in type 1 diabetic rats. At 4 weeks after the onset of diabetes, both the EFS- and exogenous acetylcholine (ACh)-induced bronchoconstriction in diabetes in vitro were greater than those in non-diabetes rats. Furthermore, endomorphin 1 (EM1) and endomorphin 2 (EM2) inhibited the response to EFS in diabetic rat isolated bronchus in a concentration- and frequency-dependent manner, which is in agreement with that in non-diabetes. However, the inhibitory effects of EMs on the EFS-induced bronchoconstriction in diabetes were significantly weaker than those in non-diabetes. Both EM1 and EM2 (1 microM) had no effect on the contractile response to exogenous ACh, indicating a prejunctional effect. Furthermore, the inhibitory effect on the EFS-induced bronchoconstriction was blocked by naloxone (10 microM). Eight weeks after the induction of diabetes, both the EFS- and exogenous ACh-induced bronchoconstrictions in diabetes were further enhanced compared to those in short-time (4 weeks) diabetic rats. Moreover, the inhibitory effects of EMs on the EFS-induced bronchoconstriction were further attenuated. These results suggest that dysfunction of presynaptic inhibitory modulation through opioid receptor by EMs may take place in the bronchus of diabetic rats.
为了评估糖尿病是否会改变μ-阿片受体（MOR）激动剂对胆碱能性支气管收缩的调节作用，我们研究了内吗啡肽（EMs）对1型糖尿病大鼠电场刺激（EFS）诱导的胆碱能性支气管收缩的抑制作用。糖尿病发病4周后，糖尿病大鼠体外EFS诱导的支气管收缩以及外源性乙酰胆碱（ACh）诱导的支气管收缩均大于非糖尿病大鼠。此外，内吗啡肽1（EM1）和内吗啡肽2（EM2）以浓度和频率依赖性方式抑制糖尿病大鼠离体支气管对EFS的反应，这与非糖尿病大鼠的情况一致。然而，EMs对糖尿病大鼠EFS诱导的支气管收缩的抑制作用明显弱于非糖尿病大鼠。EM1和EM2（1微摩尔）对外源性ACh的收缩反应均无影响，表明其作用于突触前。此外，对EFS诱导的支气管收缩的抑制作用可被纳洛酮（10微摩尔）阻断。糖尿病诱导8周后，与短期（4周）糖尿病大鼠相比，糖尿病大鼠EFS诱导的支气管收缩以及外源性ACh诱导的支气管收缩进一步增强。此外，EMs对EFS诱导的支气管收缩的抑制作用进一步减弱。这些结果表明，EMs通过阿片受体进行的突触前抑制调节功能障碍可能发生在糖尿病大鼠的支气管中。
