Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, S-751 24 Uppsala, Sweden.
Peptides. 2009 Dec;30(12):2418-22. doi: 10.1016/j.peptides.2009.08.009. Epub 2009 Aug 15.
We previously demonstrated that intracerebroventricular (i.c.v.) administration of the substance P (SP) aminoterminal fragment SP(1-7) attenuates the expression of morphine withdrawal in the male rat. In this study we have used a synthetic analogue of this peptide, i.e. the SP(1-7) amide showing higher binding potency than the native heptapeptide, in a similar experimental set-up. Thus, Wistar male rats were made tolerant to morphine by daily injections of the opiate during 8 days. Following peptide administration (i.c.v.) and a subsequent naloxone challenge a variety of physical syndromes of withdrawal were recorded. We observed that the SP(1-7) amide potently and dose-dependently reduced several signs of reaction to morphine withdrawal. Interestingly, the effect of the peptide amide was significantly attenuated by the addition of the sigma agonist (+)-SKF-10047. We conclude that the SP(1-7) amide mimics the effect of the native SP fragment and that the mechanisms for its action involve a sigma receptor site.
我们之前的研究表明，鞘内注射 P 物质（SP）氨基末端片段 SP（1-7）可减轻雄性大鼠吗啡戒断的表达。在本研究中，我们使用了该肽的一种合成类似物，即 SP（1-7）酰胺，其与天然七肽相比具有更高的结合效力，在类似的实验设置中。因此，Wistar 雄性大鼠通过每天注射阿片类药物 8 天来耐受吗啡。在给予肽（鞘内）和随后的纳洛酮挑战后，记录了各种戒断的躯体症状。我们观察到 SP（1-7）酰胺可有效且剂量依赖性地减轻对吗啡戒断的多种反应迹象。有趣的是，加入sigma 激动剂（+）-SKF-10047 可显著减弱肽酰胺的作用。我们得出结论，SP（1-7）酰胺模拟了天然 SP 片段的作用，其作用机制涉及 sigma 受体部位。
