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老年大鼠神经血管中β-肾上腺素能和毒蕈碱胆碱能受体位点密度降低。

Decreased density of beta-adrenergic and muscarinic cholinergic receptor sites in the vasa nervorum of aged rats.

作者信息

Zaccheo D, De Michele M, Mancini M, Amenta F

机构信息

Istituto di Anatomia Umana, Università di Genova, Italy.

出版信息

Mech Ageing Dev. 1991 Nov 1;60(3):255-65. doi: 10.1016/0047-6374(91)90038-2.

DOI:10.1016/0047-6374(91)90038-2
PMID:1661357
Abstract

The pharmacological profile and the anatomical localization of beta-adrenergic and muscarinic cholinergic receptors of the vasa nervorum were studied in sections of sciatic nerve using radioreceptor binding and light microscope autoradiography techniques. Sprague-Dawley rats of 4 and 24 months of age were used. [3H]Dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB) were used to label beta-adrenergic and muscarinic cholinergic receptors, respectively. The ligands were bound to sections of rat sciatic nerve in a manner consistent with the labelling of beta-adrenergic or muscarinic cholinergic receptors in the 2 age groups investigated. The dissociation constant (Kd) values (about 1.37 nM for [3H]DHA and 0.75 nM for [3H]QNB) did not significantly change between 4- and 24-month-old rats. The maximum concentration of binding sites (Bmax) for [3H]DHA was decreased by about 35% in 24 in comparison with 4-month-old rats. The Bmax value for [3H]QNB was reduced by about 50% in the aged rats. Light microscope autoradiography revealed the development of specific silver grains in the medial layer of epineurial and perineurial arteries in sections of sciatic nerve exposed either to [3H]DHA or [3H]QNB. The number of silver grains developed in epineurial and perineurial arteries of rats of 24 months is significantly lower than in animals of 4 months. The above results suggest the occurrence of an age-dependent loss in the density of beta-adrenergic and muscarinic cholinergic receptors of vasa nervorum. Vasa nervorum are the blood vessels which supply peripheral nerve trunks. They are constituted by outer (epineurial) and inner (perineurial) arteries and veins as well as by a capillary (endoneurial) plexus. Vasa nervorum are innervated by both sympathetic and non-sympathetic nerves which probably play a role in the pathogenesis of some neuropathies. Several different neurotransmitter containing nerve fibres have been identified in the vasa nervorum perivascular plexuses. However, no information is so far available concerning the neurotransmitter receptors of vasa nervorum. Moreover, although the occurrence of age-dependent changes in peripheral nerve morphology and function is well documented, very few reports were centered on the age-dependent changes of the vasa nervorum. The aims of the present study were to characterize pharmacologically and to localize anatomically the beta-adrenergic and muscarinic cholinergic receptors in the rat vasa nervorum. Moreover, the effect of ageing on the density and pattern of these receptors was investigated.

摘要

采用放射受体结合和光学显微镜放射自显影技术,在坐骨神经切片中研究了神经血管的β-肾上腺素能和毒蕈碱型胆碱能受体的药理学特征和解剖定位。使用了4个月龄和24个月龄的Sprague-Dawley大鼠。[3H]二氢阿普洛尔(DHA)和[3H]喹核醇基苯甲酸酯(QNB)分别用于标记β-肾上腺素能和毒蕈碱型胆碱能受体。配体与大鼠坐骨神经切片的结合方式与所研究的两个年龄组中β-肾上腺素能或毒蕈碱型胆碱能受体的标记一致。解离常数(Kd)值([3H]DHA约为1.37 nM,[3H]QNB约为0.75 nM)在4个月龄和24个月龄的大鼠之间没有显著变化。与4个月龄的大鼠相比,24个月龄大鼠中[3H]DHA结合位点的最大浓度(Bmax)降低了约35%。老年大鼠中[3H]QNB的Bmax值降低了约50%。光学显微镜放射自显影显示,在暴露于[3H]DHA或[3H]QNB的坐骨神经切片中,神经外膜和神经束膜动脉中层出现了特异性银颗粒。24个月龄大鼠神经外膜和神经束膜动脉中出现的银颗粒数量明显低于4个月龄的动物。上述结果表明,神经血管的β-肾上腺素能和毒蕈碱型胆碱能受体密度存在年龄依赖性损失。神经血管是供应周围神经干的血管。它们由外层(神经外膜)和内层(神经束膜)动脉和静脉以及毛细血管(神经内膜)丛组成。神经血管由交感神经和非交感神经支配,这可能在某些神经病变的发病机制中起作用。在神经血管周围丛中已鉴定出几种含有不同神经递质的神经纤维。然而,迄今为止,关于神经血管的神经递质受体尚无相关信息。此外,尽管外周神经形态和功能随年龄变化的情况已有充分记录,但很少有报告关注神经血管的年龄依赖性变化。本研究的目的是从药理学上对大鼠神经血管中的β-肾上腺素能和毒蕈碱型胆碱能受体进行表征,并从解剖学上进行定位。此外,还研究了衰老对这些受体密度和模式的影响。

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