Commons K G, van Bockstaele E J, Pfaff D W
Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, New York 10021, USA.
J Comp Neurol. 1999 Jun 14;408(4):549-59.
In the ventrolateral periaqueductal gray (PAG), endogenous pathways which dampen pain transmission can be activated by either opioids or excitatory amino acids such as N-methyl D-aspartate (NMDA). The effects of these ligands may converge, because morphine-produced analgesia in the PAG can be blocked by NMDA receptor antagonists. To determine the relationship between the subcellular sites where opioid ligands of the mu opioid receptor (MOR) and NMDA receptor ligands may act, we studied the ultrastructural distribution of immunolabeling for MOR and the R1 subunit of the NMDA receptor (NR1) in the ventrolateral PAG. MOR labeling was most commonly distributed along extrasynaptic regions of the plasma membrane of neuronal dendrites (80% or 245/306). In addition, MOR labeling was found presynaptically in axon terminals (13% or 39/306) which preferentially formed symmetric (inhibitory-type) synapses. NR1 immunoreactivity was also prevalent in dendrites (72% or 242/335), but in contrast to MOR, was usually associated with a subset of postsynaptic densities. Axon terminals (5%, 17/335) and glial processes (18%, 61/335) comprised the remainder of NR1-labeled profiles. There was a striking colocalization of MOR and NR1 labeling within dendrites. The majority of NR1-labeled dendrites contained MOR labeling (72%, 176/242) and likewise, the majority of MOR-labeled dendrites contained NR1 labeling (72%, 176/245). Thus, mu opioid and NMDA receptor ligands may act at several overlapping subcellular sites to modulate behaviors subserved by the ventrolateral PAG, such as antinociception.
在腹外侧导水管周围灰质（PAG）中，抑制疼痛传递的内源性通路可被阿片类药物或兴奋性氨基酸（如N-甲基-D-天冬氨酸（NMDA））激活。这些配体的作用可能会汇聚，因为PAG中吗啡产生的镇痛作用可被NMDA受体拮抗剂阻断。为了确定μ阿片受体（MOR）的阿片类配体和NMDA受体配体可能起作用的亚细胞位点之间的关系，我们研究了腹外侧PAG中MOR和NMDA受体（NR1）R1亚基免疫标记的超微结构分布。MOR标记最常见于神经元树突质膜的突触外区域（80%，即245/306）。此外，在轴突终末的突触前也发现了MOR标记（13%，即39/306），这些轴突终末优先形成对称（抑制型）突触。NR1免疫反应性在树突中也很普遍（72%，即242/335），但与MOR不同的是，它通常与一部分突触后致密物相关。轴突终末（5%，17/335）和胶质细胞突起（18%，61/335）构成了NR1标记轮廓的其余部分。在树突内，MOR和NR1标记有明显的共定位。大多数NR1标记的树突含有MOR标记（72%，176/242），同样，大多数MOR标记的树突也含有NR1标记（72%，176/245）。因此，μ阿片受体和NMDA受体配体可能在几个重叠的亚细胞位点起作用，以调节腹外侧PAG所介导的行为，如抗伤害感受。
