کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2537238 | 1559184 | 2006 | 6 صفحه PDF | دانلود رایگان |
Studies from our laboratory have shown that agonists at sigma1 and sigma2 receptors inhibit N-methyl-d-aspartate (NMDA)-stimulated dopamine release from motor and limbic areas of rat brain. In the current study, we examined the effects of cocaine on N-methyl-d-aspartate (NMDA)-stimulated [3H]dopamine release in rat striatal slices. Cocaine inhibited N-methyl-d-aspartate-stimulated [3H]dopamine release in a concentration-dependent manner with a Ki of approximately 10 μM, under conditions in which the dopamine transporter (DAT) was blocked by 10 μM nomifensine. The inhibition seen by cocaine was reversed by the selective σ2 antagonist 1′-[4-[1-(4-fluorophenyl)-1H-indol-3-yl]-1-butyl]-spiro[isobenzofuran-1(3H), 4′piperidine] (Lu28-179). Inhibition of release by cocaine and (+)pentazocine, under conditions in which sigma1 receptors were blocked, was also reversed by the conventional PKC inhibitor 3-[1-[3-(dimethylamino)propyl-1H-indole-3-yl]-1-H-pyrpole-2-5′-dione. These results suggest that cocaine or other agonists, acting through the σ2 receptor, require an intact conventional PKC (cPKC), most likely PKCα or PKCγ in order to inhibit dopamine release.
Journal: European Journal of Pharmacology - Volume 535, Issues 1–3, 27 March 2006, Pages 98–103