Inhibition of adenylyl cyclase 1 (AC1) and exchange protein directly activated by cAMP (EPAC) restores ATP-sensitive potassium (K
长期暴露于Gαi/o受体激动剂(如阿片类)可诱导腺苷酸环化酶(AC)敏化,导致cAMP过冲,该适应性反应被认为在阿片耐受与戒断中起关键作用。作者发现,遗传降低AC1并同时上调ATP敏感性钾通道(KATP)亚基SUR1或Kir6.2,可显著减轻吗啡耐受并减少纳洛酮诱发的戒断行为。体外研究采用EPAC2-GFP-cAMP生物传感器(cA...