Aicher S A, Schreihofer A M, Kraus J A, Sharma S, Milner T A, Guyenet P G
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA.
J Comp Neurol. 2001 Apr 23;433(1):34-47. doi: 10.1002/cne.1123.
Agonists of the mu-opioid receptor (MOR) produce profound hypotension and sympathoinhibition when microinjected into the rostral ventrolateral medulla (RVL). These effects are likely to be mediated by the inhibition of adrenergic and other presympathetic vasomotor neurons located in the RVL. The present ultrastructural studies were designed to determine whether these vasomotor neurons, or their afferents, contain MORs. RVL bulbospinal barosensitive neurons were recorded in anesthetized rats and filled individually with biotinamide by using a juxtacellular labeling method. Biotinamide was visualized by using a peroxidase method and MOR was identified by using immunogold localization of an antipeptide antibody that recognizes the cloned MOR, MOR1. The subcellular relationship of MOR1 to RVL neurons with fast- or slow-conducting spinal axons was examined by electron microscopy. Fast- and slow-conducting cells were not morphologically distinguishable. Immunogold-labeling for MOR1 was found in all RVL bulbospinal barosensitive neurons examined (9 of 9). MOR1 was present in 52% of the dendrites from both types of cells and in approximately half of these dendrites the MOR1 was at nonsynaptic plasmalemmal sites. A smaller portion of biotinamide-labeled dendrites (16%) from both types of cells were contacted by MOR1-containing axons or axon terminals. Together, these results suggest that MOR agonists can directly influence the activity of all types of RVL sympathoexcitatory neurons and that MOR agonists may also influence the activity of afferent inputs to these cells. The heterogenous distribution of MORs within individual RVL neurons indicates that the receptor is selectively targeted to specific pre- and postsynaptic sites.
将μ-阿片受体(MOR)激动剂微量注射到延髓头端腹外侧区(RVL)时,会引起严重的低血压和交感神经抑制。这些效应可能是通过抑制位于RVL的肾上腺素能和其他交感神经节前血管运动神经元介导的。目前的超微结构研究旨在确定这些血管运动神经元或其传入神经是否含有MOR。在麻醉大鼠中记录RVL延髓脊髓压力敏感神经元,并通过细胞旁标记法单独用生物素酰胺填充。使用过氧化物酶法观察生物素酰胺,使用识别克隆的MOR即MOR1的抗肽抗体的免疫金定位鉴定MOR。通过电子显微镜检查MOR1与具有快传导或慢传导脊髓轴突的RVL神经元的亚细胞关系。快传导和慢传导细胞在形态上无法区分。在所检查的所有RVL延髓脊髓压力敏感神经元(9个中的9个)中均发现了MOR1的免疫金标记。两种类型细胞的树突中有52%存在MOR1,在这些树突中约一半的MOR1位于非突触质膜部位。两种类型细胞中较小部分(16%)的生物素酰胺标记树突与含有MOR1的轴突或轴突终末接触。总之,这些结果表明MOR激动剂可直接影响所有类型的RVL交感兴奋神经元的活动,并且MOR激动剂也可能影响这些细胞的传入输入活动。MOR在单个RVL神经元内的异质分布表明该受体选择性地靶向特定的突触前和突触后位点。