In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine
In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine
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DOI：
10.1124/jpet.104.066548
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发表时间：
2004-08-01
影响因子：
3.5
通讯作者：
Unterwald, EM
中科院分区：
文献类型：
--
作者：
Muller, DL;Unterwald, EM
体外实验表明，细胞外信号调节蛋白激酶(ERKs)和Akt(又称蛋白激酶B)是阿片受体调控的众多细胞内信号分子中的两个。本研究观察了急性和慢性吗啡给药对大鼠伏隔核和尾壳核ERK和Akt激活的调节作用。通过磷酸化激活ERK和Akt，用Western印迹法检测ERK和Akt的磷酸化水平以及ERK和Akt的总蛋白水平。雄性SD大鼠接受单次注射吗啡或每天两次注射吗啡，持续6天或10天。急性吗啡后，伏隔核内PERK水平显著降低，但尾壳核中PERK水平无明显变化。单次注射吗啡后，伏隔核内磷酸化Akt水平显著升高。纳曲酮可抑制吗啡诱导的PERK下调和PACK上调。尽管服用吗啡6天后，额外津贴水平明显下降，但在10天后，额外津贴水平并没有观察到差异。与急性吗啡后的上调相反，慢性吗啡给药后伏隔核内PAKT的水平显著降低。因此，急性和慢性吗啡给药后ERK和Akt的不同激活模式对于了解体内介导阿片信号转导的其他途径具有重要意义。
In vitro evidence suggests that extracellular signal-regulated protein kinases (ERKs) and Akt (also referred to as protein kinase B) are among the myriad of intracellular signaling molecules regulated by opioid receptors. The present study examined the regulation of ERK and Akt activation in the nucleus accumbens and caudate putamen following acute and chronic morphine administration in the rat. ERK and Akt are activated by phosphorylation, hence the levels of phosphorylated ERK (pERK) and Akt (pAkt) as well as total levels of ERK and Akt protein were measured by Western blot analysis. Male Sprague-Dawley rats received either a single injection of morphine or twice daily injections of morphine for 6 or 10 days. Following acute morphine, pERK levels were significantly decreased in the nucleus accumbens but not in the caudate putamen. Phosphorylated Akt levels in the nucleus accumbens were significantly increased after a single morphine injection. Naltrexone pretreatment prevented both the morphine-induced pERK down-regulation and pAkt up-regulation. Although reductions in pERK levels were evident after 6 days of morphine administration, no differences were observed in pERK levels after 10 days. In contrast to the up-regulation seen after acute morphine, pAkt levels in the nucleus accumbens were significantly decreased after chronic morphine administration. Thus, the differential activation patterns of both ERK and Akt after acute and chronic morphine administration could have important implications for understanding additional pathways mediating opioid signaling in vivo.