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研究异丙基肾上腺素 (ISO)所致的体外培养大鼠肺 β 肾上腺素受体 ( β AR)失敏的机理 ,首先观察了不同浓度和不同作用时间的ISO对大鼠肺 β AR失敏的影响 ,可见ISO所致 β AR失敏呈良好的量 效和时 效关系 ;ISO对磷脂酶A2 (PLA2 )激活也呈时间和剂量依赖性 ,且PLA2 激活比 β AR失敏所需的ISO剂量低 .上述现象可分别被PLA2 特异性抑制剂对溴乙酰酚 (PBA)、地塞米松 (Dex)、Gi蛋白灭活剂百日咳毒素 (PTX)、抗Giα血清和抗Gβγ血清所抑制 ;而 5′ O 3 硫代三磷酸鸟甘 (GTP γ S)则能加重ISO所致β AR失敏和PLA2 激活 .以上结果提示 :体外培养的大鼠肺 β AR在激动剂长时期作用下 ,受体发生的失敏与G蛋白介导的PLA2 激活有关 ,此时β AR的信号转导途径由原来腺苷酸环化酶正偶联转变为G蛋白 βγ亚基介导的PLA2 激活
To investigate the mechanism of ISO-induced in vitro rat β-adrenergic receptor (β AR) desensitization, we first observed the effects of ISO at different concentrations and different time periods on the sensitivity of rat lung β AR ISO showed a good dose-effect and time-dependent effect on the β-AR desensitization. ISO also showed a time-and dose-dependent phospholipase A2 (PLA2) activation, and the ISO dose required for the PLA2 activation was higher than that of β AR Low.The above phenomenon can be inhibited by PLA2-specific inhibitor of PBA, Dex, Gi protein inactivator pertussis toxin (PTX), anti-Giα serum and anti-Gβγ serum respectively; ’O 3 GTP γ S could aggravate ISO-induced β-AR desensitization and PLA2 activation.The above results suggest that the rat lung β AR cultured in vitro has a long-term effect on the receptor Is related to G protein-mediated activation of PLA2, in which case the signal transduction pathway of β AR is converted from the original adenylyl cyclase into the G protein β γ subunit mediated by PLA2 activation