Aicher Sue A, Mitchell Jennifer L, Swanson Kristin C, Zadina James E
Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Brain Res. 2003 Jul 11;977(2):190-8. doi: 10.1016/s0006-8993(03)02678-7.
The endomorphins represent a novel group of endogenous opioid peptides that have high affinity for the mu-opioid receptor (MOR1). Endomorphin-2 is present in high density in the spinal and trigeminal dorsal horns and is localized to primary afferents. If endomorphin-2 were an endogenous ligand for the MOR1, we would expect to find the receptor at cellular sites in close association with the peptide. We used dual-labeling immunocytochemical methods combined with electron microscopy to determine if a cellular substrate exists for functional interactions between endomorphin-2 and MOR1. We confirmed the localization of endomorphin-2 to unmyelinated axons and axon terminals in the trigeminal dorsal horn. A small proportion of these endomorphin-2 axons contained MOR1, but many of the dendritic targets of endomorphin-2 terminals contained MOR1. Consistent with previous studies, endomorphin-2 was contained primarily in dense core vesicles and MOR1 was located primarily at non-synaptic sites. These morphological characteristics are consistent with the hypothesis that peptides are released extra-synaptically and their receptors may be located at sites distal to the synaptic junction. These anatomical data support the hypothesis that endomorphin-2 is a ligand for MORs in the trigeminal dorsal horn, particularly at postsynaptic sites.
内吗啡肽是一类新型的内源性阿片肽，对μ-阿片受体（MOR1）具有高亲和力。内吗啡肽-2在脊髓和三叉神经背角中高密度存在，并定位于初级传入神经。如果内吗啡肽-2是MOR1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方法结合电子显微镜来确定内吗啡肽-2和MOR1之间是否存在功能相互作用的细胞底物。我们证实了内吗啡肽-2在三叉神经背角的无髓轴突和轴突终末中的定位。这些内吗啡肽-2轴突中有一小部分含有MOR1，但内吗啡肽-2终末的许多树突靶点都含有MOR1。与先前的研究一致，内吗啡肽-2主要包含在致密核心囊泡中，而MOR1主要位于非突触位点。这些形态学特征与肽在突触外释放且其受体可能位于突触连接远端位点的假说一致。这些解剖学数据支持内吗啡肽-2是三叉神经背角中MOR的配体这一假说，尤其是在突触后位点。
