Rosel P, Arranz B, Vallejo J, Oros M, Crespo J M, Menchon J M, Navarro M A
Department of Clinical Chemistry, Hospital Princeps D'Espanya, Barcelona, Spain.
Psychiatry Res. 1998 Jun 30;82(3):161-70. doi: 10.1016/s0925-4927(98)00015-8.
Both the [3H]imipramine and [3H]paroxetine binding sites and the 5-HT2A receptor were simultaneously determined in frontal cortex, cingulate cortex, hippocampus and amygdala from 17 control subjects and 17 depressed suicide victims. A significant decrease in the maximum binding (Bmax) of [3H]imipramine was observed in the hippocampus of suicide victims as compared to control subjects (160 +/- 25 vs. 328 +/- 52 fmol/mg protein; P = 0.007) without changes in the apparent affinity constant (Kd). Furthermore, a significant decrease in the number of 5-HT2A binding sites, together with a significantly lower Kd, was also observed in the hippocampus of suicides as compared to control subjects (129 +/- 18 vs. 225 +/- 32 fmol/mg protein; P = 0.02 and 0.91 +/- 0.07 vs. 1.38 +/- 0.08 nM, respectively; P = 0.006). [3H]Paroxetine binding did not display modifications between the two groups in either Bmax or Kd from any of the brain regions studied. When all four brain regions were taken together, a down-regulation was noted between presynaptic [3H]imipramine binding and the postsynaptic 5-HT2A receptor (r = -0.40; P = 0.0013) in the control group. This correlation did not appear in the suicide group. No correlation was observed between [3H]paroxetine binding and the 5-HT2A receptor in either control subjects or suicides. Taken together, these results suggest that the 5-HT uptake site measured with [3H]imipramine and the 5-HT2A receptors are reliable markers of serotonergic dysfunction.
在17名对照受试者和17名抑郁自杀受害者的额叶皮质、扣带回皮质、海马体和杏仁核中，同时测定了[³H]丙咪嗪和[³H]帕罗西汀结合位点以及5-HT₂A受体。与对照受试者相比，自杀受害者海马体中[³H]丙咪嗪的最大结合量（Bmax）显著降低（160±25对328±52 fmol/mg蛋白质；P = 0.007），而表观亲和力常数（Kd）无变化。此外，与对照受试者相比，自杀者海马体中5-HT₂A结合位点数量也显著减少，同时Kd显著降低（分别为129±18对225±32 fmol/mg蛋白质；P = 0.02和0.91±0.07对1.38±0.08 nM；P = 0.006）。在所研究的任何脑区中，[³H]帕罗西汀结合在两组之间的Bmax或Kd均未显示出改变。当将所有四个脑区综合考虑时，对照组中突触前[³H]丙咪嗪结合与突触后5-HT₂A受体之间存在下调（r = -0.40；P = 0.0013）。这种相关性在自杀组中未出现。在对照受试者或自杀者中，均未观察到[³H]帕罗西汀结合与5-HT₂A受体之间的相关性。综上所述，这些结果表明，用[³H]丙咪嗪测量的5-HT摄取位点和5-HT₂A受体是5-羟色胺能功能障碍的可靠标志物。
