低pH处理对阿片受体激动剂调节cAMP第二信使系统的作用(英文)

Effects of low-pH treatment on cAMP second messenger system regulated by different opioid agonists

研究不同的阿片类物质对ＣＡＭＰ第二信使系统不同作用的机制．方法：用低 ｐＨ方法失活 Ｇｓ蛋白，用蛋白竞争法测ＮＧ１０８－１５细胞膜腺苷酸环化酶（ＡＣ）活性．结果：与二氢埃托啡（ＤＨＥ）和埃托啡（Ｅｔｏ）不同，低ｐＨ处理明显增加吗啡（ Ｍｏｒ）和美沙酮（Ｍｅｔ）对正常和自身慢性处理细胞的膜ＡＣ活性的抑制作用．与Ｍｏｒ等不同，ＤＨＥ和Ｅｔｏ对自身慢性处理细胞的膜ＡＣ活性抑制作用降低不明显，纳洛酮催促， ＤＨＥ和Ｅｔｏ慢性处理细胞的膜ＡＣ活性也未见显著反跳性升高．低ｐＨ处理使纳洛酮催促的Ｍｏｒ慢性处理细胞的膜ＡＣ活性反跳性升高作用消失。结论：不同的阿片类ＣＡＭＰ信使系统的不同作用与它们对Ｇｓ功能调节差异有关，Ｇｓ与阿片类物质的耐受和依赖密切相关。

AIM: To study the mechanism of opioid agonists in regulation of cAMP second messenger system. METHODS: Low-pH treatment was used to deplete the stimulatory G portein (Gs ) function. The effects of some opiates on adenylate cyclase were compared between control and low-pH treatment membranes. RESULTS: In contrast to dihydroetorphine (DHE), etorphine (Eto ), morphine (Mor) and methadone (Met) substantially increased the inhibitory effects on adenylate cyclase in membranes Prepared from naive and chronic Mor- or Met-treated NG108-15 cells by low-pH treatment. In contrast to Mor, DHE and Eto did not result in significant decrease in the inhibitory effects on adenylate cyclase in membranes from the cells treated chronically with DHE or Eto. Marked rebound of adenylate cyclase was also not observed in membranes from chronic DHE or Eto-treated cells when precipitated with naloxone. Low-pH treatment eliminated naloxone-induced rebound of adenylate cyclase in chronic Mor-treated cells. CONCLUSION: The difference in opiate-induced functional adaptive alteration of Gs is at least one biochemical mechanism of developing opiate tolerance and dependence.