What are the roles of substance P and neurokinin-1 receptors in the control of negative chronotropic or negative dromotropic vagal motoneurons? A physiological and ultrastructural analysis.
What are the roles of substance P and neurokinin-1 receptors in the control of negative chronotropic or negative dromotropic vagal motoneurons? A physiological and ultrastructural analysis.
复制标题
P 物质和神经激肽-1 受体在控制负变时性或负向变时性迷走神经运动神经元中的作用是什么？
DOI：
10.1016/0006-8993(95)01583-3
复制
发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Gatti,PJ
中科院分区：
文献类型：
--
作者：
Massari,VJ;Johnson,TA;Gillis,RA;Gatti,PJ
最近的资料表明，在疑核（NA）中存在负性变时性和负性变导性神经元的心脏定位组织。负性传导神经元在头侧腹外侧NA（rNA-VL）中发现，负性变时神经元在尾侧腹外侧NA（cNA-VL）中发现，并且这两种类型的神经元在腹外侧NA（iNA-VL）的中间水平中发现。P物质（SP）免疫反应阳性神经末梢与iNA-VL中负性变时性迷走运动神经元形成突触，NA中微量注射SP引起心动过缓。本文试图：（1）确定介导SP在iNA-VL内微量注射负性变时效应的速激肽受体类型，（2）确定选择性SP激动剂在rNA-VL内微量注射对房室传导的生理效应，（3）确定在rNA-VL内微量注射SP对房室传导的影响。（3）在rNA-VL区发现SP免疫反应阳性神经末梢与负向传导迷走运动神经元的突触相互作用的超微结构证据。将兴奋性氨基酸谷氨酸（Glu）微量注射到iNA-VL中以激活所有局部迷走神经节前神经元，引起心动过缓和AV传导率降低。注射选择性神经激肽-1（NK-1）受体激动剂药物GR-73632也引起心动过缓，但是激动剂诱导的脱敏的快速发作阻止了对iNA-VL中AV传导的潜在影响的评价。这些数据表明，SP诱导的心动过缓，可以引起从NA介导的，至少部分，由NK-1受体。微量注射Glu到rNA-VL引起AV传导减少，而不影响心率。另一方面，GR-73632微量注射到rNA-VL中不影响AV传导。将霍乱毒素β亚单位与辣根过氧化物酶（CTB-HRP）结合后注射到选择性介导AV传导变化的左心房脂肪垫神经节中，在rNA-VL中进行逆行标记神经元的组织化学观察。这些组织随后进行处理的同时SP免疫细胞化学可视化，并通过电子显微镜检查。组织化学标记的神经元大，多极，丰富的细胞质含有大量的粗面内质网，并表现出独特的树突和体棘。未标记的神经末梢与组织化学标记的神经元的树突、树突棘和胞体形成不对称或对称的突触。SP免疫反应阳性神经末梢也被检测到的rNA-VL。SP终端通常包含许多小的多形性囊泡，多个大的致密的核心囊泡，和几个线粒体，他们突触后未标记的树突状配置文件。共观察到154 SP免疫反应神经末梢的组织，其中也包含组织化学标记的配置文件的显微照片。在检查的切片上，没有一个突触具有逆行标记的轮廓。总之，生理和超微结构的数据表明，SP终端在iNA-VL修改负变时性迷走运动神经元的输出。这种作用是由NK-1受体介导的。另一方面，生理和超微结构的数据表明，SP终端在rNA-VL不修改负向传导迷走神经运动神经元的输出。因此，不同的机制（神经递质或受体）介导心率和AV传导的中枢迷走神经控制。
Recent data indicate that there is a cardiotopic organization of negative chronotropic and negative dromotropic neurons in the nucleus ambiguus (NA). Negative dromotropic neurons are found in the rostral ventrolateral NA (rNA-VL), negative chronotropic neurons are found in the caudal ventrolateral NA (cNA-VL), and both types of neurons are found in an intermediate level of the ventrolateral NA (iNA-VL). Substance P (SP) immunoreactive nerve terminals synapse upon negative chronotropic vagal motoneurons in the iNA-VL, and SP microinjections in the NA cause bradycardia. In the present report we have attempted to: (1) define the type of tachykinin receptor which mediates the negative chronotropic effect of SP microinjections into the iNA-VL; (2) define the physiological effect of microinjections of a selective SP agonist into the rNA-VL on atrioventricular (AV) conduction; and (3) find ultrastructural evidence for synaptic interactions of SP-immunoreactive nerve terminals with negative dromotropic vagal motoneurons in the rNA-VL. Microinjections of the excitatory amino acid glutamate (Glu) into the iNA-VL to activate all local vagal preganglionic neurons caused both bradycardia and a decrease in the rate of AV conduction. Injections of the selective neurokinin-1 (NK-1) receptor agonist drug GR-73632 also caused bradycardia, however the rapid onset of agonist induced desensitization prevented an evaluation of potential effects on AV conduction in the iNA-VL. These data suggest that the SP-induced bradycardia which can be elicited from the NA is mediated, at least in part, by NK-1 receptors. Microinjections of Glu into the rNA-VL caused a decrease in AV conduction without an effect on cardiac rate. On the other hand, GR-73632 microinjections into rNA-VL did not affect AV conduction. Following injections of the β subunit of cholera toxin conjugated to horseradish peroxidase (CTB-HRP) into the left atrial fat pad ganglion which selectively mediates changes in AV conduction, retrogradely labeled neurons were histochemically visualized in the rNA-VL. These tissues were subsequently processed for the simultaneous immunocytochemical visualization of SP, and examined by electron microflapy. Histochemically labeled neurons were large, multipolar, with abundant cytoplasm containing large masses of rough endoplasmic reticulum, and exhibited distinctive dendritic and somatic spines. Unlabeled nerve terminals were noted to form either asymmetric or symmetric synapses with dendrites, dendritic spines, and perikarya of histochemically labeled neurons. SP-immunoreactive nerve terminals were also detected in the rNA-VL. SP terminals typically contained numerous small pleomorphic vesicles, multiple large dense core vesicles, and several mitochondria, and they synapsed upon unlabeled dendritic profiles. A total of 154 SP-immunoreactive nerve terminals were observed on photomicrographs of tissues which also contained histochemically labeled profiles. None made an identifiable synapse with a retrogradely labeled profile on the sections examined. In summary, both physiological and ultrastructural data indicate that SP terminals in the iNA-VL do modify the output of negative chronotropic vagal motoneurons. This effect is mediated by NK-1 receptors. On the other hand both physiological and ultrastructural data indicate that SP terminals in the rNA-VL do not modify the output of negative dromotropic vagal motoneurons. Therefore different mechanisms (neurotransmitters or receptors) mediate the central vagal control of cardiac rate and AV conduction.