Stefano G B, Zukin R S, Kream R M
J Pharmacol Exp Ther. 1982 Sep;222(3):759-64.
Considerable evidence has demonstrated an interrelationship between the enkephalinergic and dopaminergic systems in both the mammalian and invertebrate nervous systems. We have described recently the presence of two classes of high affinity opiate binding sites in the nervous tissue of the marine mollusc Mytilus edulis. In order to examine the physiological role of these high affinity opiate sites, M. edulis pedal ganglia (Pg) were treated with the selective neurotoxin 6-hydroxydopamine (1 micrograms/animal, applied topically to the intact Pg); animals were sacrificed 5 days after treatment. The dopamine content of the Pg from lesioned animals was reduced to 33% relative to that of Pg from control animals. Neither serotonin nor norepinephrine levels were reduced. Fluorescent micrographs of formaldehyde-treated Pg from both lesioned and control animals revealed that the neurotoxic substance accumulates in the synaptically rich neuropil and not in the cortex of the Pg. Thus, the partial reduction in dopamine levels may reflect nearly total loss of dopamine in terminals with essentially no change in the nerve cell bodies. High affinity binding of the potent opioid peptide 125I-labeled FK 33-824 (2 nM) was reduced by 81% and low affinity binding (10 nM peptide) by 43% in Pg from lesioned animals relative to that in control tissue. In addition, D-Ala2-Met5-enkephalin, beta-endorphin and etorphine failed to change dopamine levels in lesioned animals. Together, these results suggest that the high affinity opiate binding sites that mediate alteration in dopamine levels are on dopaminergic presynaptic terminals.
大量证据表明,在哺乳动物和无脊椎动物的神经系统中,脑啡肽能系统和多巴胺能系统之间存在相互关系。我们最近报道了在海洋软体动物紫贻贝的神经组织中存在两类高亲和力阿片结合位点。为了研究这些高亲和力阿片位点的生理作用,用选择性神经毒素6-羟基多巴胺(1微克/动物,局部应用于完整的足神经节)处理紫贻贝的足神经节;处理后5天处死动物。与对照动物的足神经节相比,受损动物足神经节中的多巴胺含量降低至33%。5-羟色胺和去甲肾上腺素水平均未降低。对受损和对照动物经甲醛处理的足神经节进行荧光显微照片显示,神经毒性物质积聚在富含突触的神经纤维网中,而不是在足神经节的皮质中。因此,多巴胺水平的部分降低可能反映了终末中多巴胺几乎完全丧失,而神经细胞体基本没有变化。与对照组织相比,受损动物足神经节中强效阿片肽125I标记的FK 33-824(2 nM)的高亲和力结合降低了81%,低亲和力结合(10 nM肽)降低了43%。此外,D-丙氨酸2-甲硫氨酸5-脑啡肽、β-内啡肽和埃托啡未能改变受损动物的多巴胺水平。这些结果共同表明,介导多巴胺水平改变的高亲和力阿片结合位点位于多巴胺能突触前终末。