Intraepithelial vagal sensory nerve terminals in rat pulmonary neuroepithelial bodies express P2X3 receptors
Intraepithelial vagal sensory nerve terminals in rat pulmonary neuroepithelial bodies express P2X3 receptors
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DOI：
10.1165/ajrcmb.23.1.3936
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发表时间：
2000-07-01
影响因子：
6.4
通讯作者：
Timmermans, JP
中科院分区：
文献类型：
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作者：
Brouns, I;Adriaensen, D;Timmermans, JP
参与肺神经上皮小体（NEB）与其神经支配的迷走感觉成分之间相互作用的神经递质/调节剂尚未阐明，因为已知P2 X（3）嘌呤受体在外周感觉神经元中强烈表达，本研究的目的是检测表达P2 X（3）的神经末梢的定位一般来说，大鼠肺中的嘌呤受体，特别是那些接触肺NEB的嘌呤受体。最引人注目的是上皮内P2 X（3）嘌呤受体免疫反应（IR）神经末梢的分支，在所有情况下，这些神经末梢似乎都在降钙素基因相关肽（CGRP）或钙结合素D28 k（CB）标记的NEB细胞之间分叉。然而，并非所有NEB都接受表达P2 X（3）受体的神经末梢。用CGRP和CB染色作为NEBs神经支配的两种不同感觉成分的标记物，发现P2 X（3）受体和CB免疫反应性共定位，而CGRP-IR纤维明显形成不同的群体。在迷走神经结下挤压后，与NEB接触的特征性P2 X（3）受体阳性神经纤维消失，并且在逆行追踪实验中，示踪剂和P2 X（3）受体免疫反应性在迷走神经结状神经元胞体中共定位，进一步支持了我们的假设，即与NEB接触的P2 X（3）受体阳性神经纤维起源于迷走神经感觉结状神经节。奎纳克林在NEB中的蓄积（提示其分泌囊泡中存在高浓度的三磷酸腺苷（ATP））和P2 X（3）受体染色的结合表明，大鼠肺中的分支上皮内P2 X（3）受体IR神经末梢仅与奎纳克林染色的NEB相关。我们的结论是，ATP可能通过P2 X（3）受体介导的途径在NEBs的迷走感觉神经支配中作为神经递质/神经调质。需要进一步研究以确定表达P2 X（3）受体的神经元，特别是支配大鼠肺中NEB的神经元，是否属于P2 X（3）受体IR伤害性迷走结状神经元的群体。
The neurotransmitters/modulators involved in the interaction between pulmonary neuroepithelial bodies (NEBs) and the vagal sensory component of their innervation have not yet been elucidated, Because P2X(3) purinoreceptors are known to be strongly expressed in peripheral sensory neurons, the aim of the present study was to examine the localization of nerve endings expressing P2X(3) purinoreceptors in the rat lung in general and those contacting pulmonary NEBs in particular. Most striking were intraepithelial arborizations of P2X(3) purinoceptor-immunoreactive (IR) nerve terminals, which in all cases appeared to ramify between calcitonin gene-related peptide (CGRP)- or calbindin D28k (CB)-labeled NEB cells. However, not all NEBs received nerve endings expressing P2X(3) receptors. Using CGRP and CB staining as markers for two different sensory components of the innervation of NEBs, it was revealed that P2X(3) receptor and CB immunoreactivity were colocalized, whereas CGRP-IR fibers clearly formed a different population. The disappearance of characteristic P2X(3) receptor-positive nerve fibers in contact with NEBs after infra-nodosal vagal crush and colocalization of tracer and P2X(3) receptor immunoreactivity in vagal nodose neuronal cell bodies in retrograde tracing experiments further supports our hypothesis that the P2X(3) receptor-IR nerve fibers contacting NEBs have their origin in the vagal sensory nodose ganglia. Combination of quinacrine accumulation in NEBs, suggestive of the presence of high concentrations of adenosine triphosphate (ATP) in their secretory vesicles, and P2X(3) receptor staining showed that the branching intraepithelial P2X(3) receptor-IR nerve terminals in rat lungs were exclusively associated with quinacrine-stained NEBs. We conclude that ATP might act as a neurotransmitter/neuromodulator in the vagal sensory innervation of NEBs via a P2X(3) receptor-mediated pathway. Further studies are necessary to determine whether the P2X(3) receptor-expressing neurons, specifically innervating NEBs in the rat lung, belong to a population of P2X(3) receptor-IR nociceptive vagal nodose neurons.