In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine

被引:89
|
作者
Muller, DL
Unterwald, EM
机构
[1] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA
[2] Temple Univ, Sch Med, Ctr Subst Abuse Res, Philadelphia, PA 19140 USA
[3] Rockefeller Univ, New York, NY 10021 USA
来源
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 2004年 / 310卷 / 02期
关键词
D O I
10.1124/jpet.104.066548
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页码:774 / 782
页数:9
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