Developmental Expression of δ-Opioid Receptors During Maturation of the Parasympathetic, Sympathetic, and Sensory Innervations of the Neonatal Heart: Early Targets for Opioid Regulation of Autonomic Control
Developmental Expression of δ-Opioid Receptors During Maturation of the Parasympathetic, Sympathetic, and Sensory Innervations of the Neonatal Heart: Early Targets for Opioid Regulation of Autonomic Control
复制标题
DOI：
10.1002/cne.22560
复制
发表时间：
2011-04-01
影响因子：
2.5
通讯作者：
Abdul-Khaliq, Hashim
中科院分区：
文献类型：
--
作者：
Mousa, Shaaban A.;Shaqura, Mohammed;Abdul-Khaliq, Hashim
关于局部阿片类药物调节心脏功能的证据正在积累。然而，δ-阿片受体（DORs）的确切解剖位置和表达过程中的自主神经和感觉神经支配的新生儿心脏的成熟是未知的。因此，我们的目的是在出生后第1天（P），P7和成年期（P56-P84）的新生大鼠心脏心内神经节中表征阿片类药物的靶位点。大鼠心房进行逆转录聚合酶链反应，蛋白质印迹，放射性配体结合，和免疫荧光共聚焦分析DORs与神经元标记物囊泡乙酰胆碱转运蛋白（VAChT），酪氨酸羟化酶（TH），降钙素基因相关肽（CGRP），和P物质（SP）。我们的研究结果表明，DOR的mRNA，蛋白质和结合位点，从P1逐渐增加到成年。免疫荧光共聚焦显微镜显示DOR与VAChT共定位于大直径的主神经元、TH免疫反应（IR）小的强荧光（SIF）儿茶酚胺能细胞和CGRP或SP-IR传入神经末梢在心内神经节和心房心肌内分叉。DOR与VAChT-IR神经元的共表达从出生第一天（P1）开始观察。相反，在P1的心内神经节中未观察到TH-IR SIF细胞或CGRP-IR纤维上的DOR，但在P7大鼠中观察到DOR。从新生儿到成年，心房肌中与不同神经元标记物共表达DORs的神经纤维密度增加。总之，增强的DOR表达平行于心脏的副交感神经、交感神经和感觉神经支配的成熟，表明心脏阿片系统是通过自主神经系统对新生儿和成人心脏功能的重要调节器。神经学比较杂志519：957-971，2011。(C)2010 Wiley-Liss，Inc.
Evidence is accumulating regarding the local opioid regulation of heart function. However, the exact anatomical location of delta-opioid receptors (DORs) and expression during maturation of the autonomic and sensory innervations of the neonatal heart is unknown. Therefore, we aimed to characterize target sites for opioids in neonatal rat heart intracardiac ganglia at postnatal day (P)1, P7 and adulthood (P56-P84). Rat heart atria were subjected to reverse-transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis of DORs with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), and substance P (SP). Our results demonstrated DOR mRNA, protein, and binding sites that gradually increased from P1 toward adulthood. Immunofluorescence confocal microscopy showed DOR co-localized with VAChT in large-diameter principal neurons, TH-immunoreactive (IR) small intensely fluorescent (SIF) catecholaminergic cells, and CGRP-or SP-IR afferent nerve terminals arborizing within intracardiac ganglia and atrial myocardium. Co-expression of DOR with VAChT-IR neurons was observed from the first day of birth (P1). In contrast, DORs on TH-IR SIF cells or CGRP-IR fibers were not observed in intracardiac ganglia of P1, but rather in P7 rats. The density of nerve fibers in atrial myocardium co-expressing DORs with different neuronal markers increased from neonatal age toward adulthood. In summary, the enhanced DOR expression parallel to the maturation of cardiac parasympathetic, sympathetic, and sensory innervation of the heart suggests that the cardiac opioid system is an important regulator of neonatal and adult heart function through the autonomic nervous system. J. Comp. Neurol. 519:957-971, 2011. (C) 2010 Wiley-Liss, Inc.