Ding Y Q, Kaneko T, Nomura S, Mizuno N
Department of Morphological Brain Science, Faculty of Medicine, Kyoto University, Japan.
J Comp Neurol. 1996 Apr 8;367(3):375-402. doi: 10.1002/(SICI)1096-9861(19960408)367:3<375::AID-CNE5>3.0.CO;2-2.
Of the three major types of opioid receptors ( mu, delta, kappa) in the nervous system, mu-opioid receptor shows the highest affinity for morphine that exerts powerful effects on nociceptive, autonomic, and psychological functions. So far, at least two isoforms of mu-opioid receptors have been cloned from rat brain. The present study attempted to examine immunohistochemically the distribution of mu-opioid receptors in the rat central nervous system with two kinds of antibodies to recently cloned mu-opioid receptors (MOR1 and MOR1B). One antibody recognized a specific site for MOR1, and the other bound to a common site for MOR1 and MOR1B. Intense MOR1-like immunoreactivity (LI) was seen in the 'patch' areas and subcallosal streak in the striatum, medial habenular nucleus, medial terminal nucleus of the accessory optic tract, interpeduncular nucleus, median raphe nucleus, parabrachial nuclei, locus coeruleus, ambiguous nucleus, nucleus of the solitary tract, and laminae I and II of the medullary and spinal dorsal horns. Many other regions, including the cerebral cortex, amygdala, thalamus, and hypothalamus, also contained many neuronal elements with MOR1-LI. The distribution pattern of the immunoreactivity revealed with the antibody to the common site for MOR1 and MOR1B (MOR1/1B-LI) was almost the same as that of MOR1-LI. Both MOR1-LI and MOR1/1B-LI were primarily located in neuronal cell bodies and dendrites. However, the immunoreactivities were observed in the accessory optic tract, fasciculus retroflexus, solitary tract, and primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns. The presynaptic location of MOR1-LI and MOR1/1B-LI was confirmed by lesion experiments: Enucleation, placing a lesion in the medial habenular nucleus, removal of the nodose ganglion, or dorsal rhizotomy resulted in a clear reduction of the immunoreactivities, respectively, in the nuclei of the accessory optic tract, some subnuclei of the interpeduncular nucleus, nucleus of the solitary tract, or laminae I and II of the spinal dorsal horn. The results indicate that the mu-opioid receptors are widely distributed in the brain and spinal cord, mainly postsynaptically and occasionally presynaptically. Opioids, including morphine, may inhibit the excitation of neurons via the postsynaptic mu-opioid receptors, and also suppress the release of neurotransmitters and/or neuromodulators from axon terminals through the presynaptic mu-opioid receptors.
在神经系统的三种主要阿片受体类型（μ、δ、κ）中，μ-阿片受体对吗啡具有最高亲和力，吗啡对伤害感受、自主神经和心理功能发挥强大作用。到目前为止，已从大鼠脑中克隆出至少两种μ-阿片受体亚型。本研究试图用两种针对最近克隆的μ-阿片受体（MOR1和MOR1B）的抗体，通过免疫组织化学方法检测大鼠中枢神经系统中μ-阿片受体的分布。一种抗体识别MOR1的特定位点，另一种与MOR1和MOR1B的共同位点结合。在纹状体的“斑块”区域和胼胝体下纹、内侧缰核、副视束内侧终核、脚间核、中缝正中核、臂旁核、蓝斑、疑核、孤束核以及延髓和脊髓背角的I层和II层中可见强烈的MOR1样免疫反应性（LI）。许多其他区域，包括大脑皮层、杏仁核、丘脑和下丘脑，也含有许多具有MOR1-LI的神经元成分。用针对MOR1和MOR1B共同位点的抗体（MOR1/1B-LI）显示的免疫反应性分布模式与MOR1-LI几乎相同。MOR1-LI和MOR1/1B-LI主要位于神经元细胞体和树突中。然而，在副视束、后屈束、孤束以及延髓和脊髓背角浅层的初级传入纤维中也观察到了免疫反应性。通过损伤实验证实了MOR1-LI和MOR1/1B-LI的突触前定位：摘除眼球、在内侧缰核放置损伤、切除结节神经节或背根切断术分别导致副视束核、脚间核的一些亚核、孤束核或脊髓背角I层和II层中的免疫反应性明显降低。结果表明，μ-阿片受体广泛分布于脑和脊髓中，主要位于突触后，偶尔位于突触前。包括吗啡在内的阿片类药物可能通过突触后μ-阿片受体抑制神经元的兴奋，也可能通过突触前μ-阿片受体抑制神经递质和/或神经调质从轴突终末的释放。
