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

Zhongguo yao li xue bao = Acta pharmacologica Sinica Pub Date : 1999-06-01

J G Liu, Z H Gong, B Y Qin

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Abstract

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 protein (Gs) function. The effects of some opiates on adenylate cyclase were compared between control and low-pH treatment membranes.

Results: In contrast to dehydroetorphine (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.

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低ph处理对不同阿片激动剂调控cAMP第二信使系统的影响。

目的:探讨阿片受体激动剂调控cAMP第二信使系统的作用机制。方法:采用低ph处理，降低刺激G蛋白(Gs)功能。比较了几种阿片类药物对对照膜和低ph处理膜中腺苷酸环化酶的影响。结果:与脱氢埃托啡(DHE)相比，埃托啡(Eto)、吗啡(Mor)和美沙酮(Met)在低ph条件下显著增强了Mor或Met处理的NG108-15细胞膜对腺苷酸环化酶的抑制作用。与Mor相比，DHE和Eto对慢性DHE或Eto处理的细胞膜中腺苷酸环化酶的抑制作用没有显著降低。当纳洛酮沉淀时，慢性DHE或eto处理的细胞的膜中也未观察到腺苷酸环化酶的明显反弹。低ph处理消除了纳洛酮诱导的慢性莫尔处理细胞中腺苷酸环化酶的反弹。结论:阿片类药物诱导的Gs功能适应性改变的差异是阿片类药物耐受和依赖发生的至少一种生化机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Zhongguo yao li xue bao = Acta pharmacologica Sinica

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