Silverman M B, Hermes S M, Zadina J E, Aicher S A
Oregon Health & Science University, Neurological Sciences Institute, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA.
Neuroscience. 2005;135(3):887-96. doi: 10.1016/j.neuroscience.2005.06.072. Epub 2005 Sep 8.
Endomorphins represent a group of endogenous opioid peptides with high affinity for the mu-opioid receptor. In the brainstem, Endomorphin-2 is found in trigeminal dorsal horn and the nuclei of the solitary tract, suggesting its presence in both nociceptive and visceral primary afferents. If Endomorphin-2 were an endogenous ligand for the mu-opioid receptor, we would expect to find the receptor at cellular sites in close association with the peptide. We used dual-labeling immunocytochemistry combined with electron microscopy to examine interactions between Endomorphin-2-immunoreactive and mu-opioid receptor-immunoreactive profiles within the nuclei of the solitary tract in the rat. Endomorphin-2-immunoreactivity was found primarily in unmyelinated axons and axon terminals in nuclei of the solitary tract and the majority of these terminals contained dense core vesicles. Endomorphin-2-immunoreactive axon terminals often formed asymmetric synapses with dendritic spines lacking mu-opioid receptor-immunoreactivity, but mu-opioid receptor-immunoreactivity was found in many of the larger dendritic targets of Endomorphin-2-immunoreactive terminals. Thus, mu-opioid receptor-immunoreactivity was found in the postsynaptic targets of Endomorphin-2-immunoreactive axon terminals, consistent with the hypothesis that Endomorphin-2 is an endogenous ligand for this receptor within the nuclei of the solitary tract. A small number of Endomorphin-2-immunoreactive somata, dendrites, and axon terminals also contained mu-opioid receptor-immunoreactivity. Cells that contain both the opioid peptide and its receptor may be a substrate for potential autoregulation of nuclei of the solitary tract neurons by opioid ligands. Finally, using tract tracing and confocal microscopy, we found Endomorphin-2-immunoreactivity in a subset of vagal afferents. Together these findings support the hypothesis that Endomorphin-2 is a ligand for the mu-opioid receptor within nuclei of the solitary tract and that the peptide is at least partially derived from primary visceral afferents.
内吗啡肽是一类对μ-阿片受体具有高亲和力的内源性阿片肽。在脑干中，内吗啡肽-2存在于三叉神经背角和孤束核中，表明其存在于伤害性和内脏初级传入神经中。如果内吗啡肽-2是μ-阿片受体的内源性配体，我们预期会在与该肽紧密相关的细胞位点发现该受体。我们使用双标记免疫细胞化学结合电子显微镜来检查大鼠孤束核内免疫反应性内吗啡肽-2和免疫反应性μ-阿片受体之间的相互作用。内吗啡肽-2免疫反应性主要存在于孤束核中的无髓轴突和轴突终末，并且这些终末中的大多数含有致密核心囊泡。内吗啡肽-2免疫反应性轴突终末常与缺乏μ-阿片受体免疫反应性的树突棘形成不对称突触，但在许多内吗啡肽-2免疫反应性终末的较大树突靶点中发现了μ-阿片受体免疫反应性。因此，在免疫反应性内吗啡肽-2轴突终末的突触后靶点中发现了μ-阿片受体免疫反应性，这与内吗啡肽-2是孤束核内该受体的内源性配体这一假设一致。少数内吗啡肽-2免疫反应性胞体、树突和轴突终末也含有μ-阿片受体免疫反应性。同时含有阿片肽及其受体的细胞可能是阿片配体对孤束核神经元进行潜在自动调节的底物。最后，通过束路追踪和共聚焦显微镜检查，我们在一部分迷走神经传入纤维中发现了内吗啡肽-2免疫反应性。这些发现共同支持了这样的假设，即内吗啡肽-2是孤束核内μ-阿片受体的配体，并且该肽至少部分源自初级内脏传入神经。
