Iverfeldt K, Ogren S O, Bartfai T
Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, Sweden.
Acta Physiol Scand. 1988 Feb;132(2):175-9. doi: 10.1111/j.1748-1716.1988.tb08315.x.
Substance P receptors were examined in crude synaptosomal fraction preparations of the rat spinal cord using [125I]Bolton Hunter Substance P ([125I]BHSP) which binds with an affinity of 0.043 +/- 0.015 nM. The concentration of binding sites in the dorsal and in the ventral part was 4.55 +/- 0.86 and 2.35 +/- 0.35 fmol mg-1, respectively. GTP inhibited the specific binding of [125I]BHSP in a concentration dependent manner, with 10(-3) mol l-1 GTP yielding 89-90% inhibition and 10(-5) mol l-1 GTP producing 50% inhibition. This value was similar in dorsal and ventral spinal cord. The effects on SP receptors of chronic treatment with the tricyclic antidepressant imipramine (2 x 10 mumol kg-1 day-1 p.o. 14 days) and the specific 5-HT (serotonin) uptake blockers alaproclate (2 x 20 mumol kg-1 day-1 p.o. 14 days) and zimelidine (2 x 10 mumol kg-1 day-1 p.o. 14 days) were examined in the ventral spinal cord, where SP and 5-HT coexist in the terminals of descending neurons from the raphe nucleus. Zimelidine treatment was found to cause a significant reduction in the number of substance P binding sites in the rat ventral spinal cord as compared to saline treated controls. These findings are discussed in light of the previous observation (Brodin et al. 1984) that SP levels are significantly elevated after treatment with antidepressant drugs especially with zimelidine, which alters the firing rates of 5-HT and 5-HT/SP neurons.
使用[125I]博尔顿·亨特P物质（[125I]BHSP），其结合亲和力为0.043±0.015 nM，对大鼠脊髓粗制突触体部分制剂中的P物质受体进行了检测。背侧和腹侧部分的结合位点浓度分别为4.55±0.86和2.35±0.35 fmol mg-1。GTP以浓度依赖性方式抑制[125I]BHSP的特异性结合，10(-3) mol l-1 GTP产生89 - 90%的抑制作用，10(-5) mol l-1 GTP产生50%的抑制作用。该值在脊髓背侧和腹侧相似。在腹侧脊髓中研究了三环类抗抑郁药丙咪嗪（2×10 μmol kg-1每日口服，共14天）、特异性5-羟色胺（5-羟色胺）摄取阻滞剂阿普氯胺（2×20 μmol kg-1每日口服，共14天）和齐美利定（2×10 μmol kg-1每日口服，共14天）对SP受体的慢性治疗效果，在腹侧脊髓中，P物质和5-羟色胺共存于中缝核下行神经元的终末。与盐水处理的对照组相比，发现齐美利定治疗导致大鼠腹侧脊髓中P物质结合位点数量显著减少。根据先前的观察结果（Brodin等人，1984年）对这些发现进行了讨论，即抗抑郁药尤其是齐美利定治疗后P物质水平显著升高，这改变了5-羟色胺和5-羟色胺/P物质神经元的放电率。
