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大鼠迷走神经中腺苷A1受体轴突运输的放射自显影可视化以及高血压和正常血压大鼠迷走神经复合体中腺苷A1受体结合的表征。

Autoradiographic visualisation of axonal transport of adenosine A1 receptors along the rat vagus nerve and characterisation of adenosine A1 receptor binding in the dorsal vagal complex of hypertensive and normotensive rats.

作者信息

Krstew E, Jarrott B, Lawrence A J

机构信息

Department of Pharmacology, Monash University, Clayton, Victoria, Australia.

出版信息

Brain Res. 1998 Aug 17;802(1-2):61-8. doi: 10.1016/s0006-8993(98)00567-8.

Abstract

The present study had employed in vitro receptor autoradiography with [3H]DPCPX to visualise the presence of adenosine A1 receptors on the rat nodose ganglion, which contains the perikarya of vagal afferent neurons projecting the the nucleus tractus solitarius (NTS). In addition, unilateral vagal ligation resulted in an accumulation of [3H]DPCPX binding adjacent to the ligatures, indication that adenosine A1 receptors are subject to axoplasmic flow along the rat vagus nerve. Radioligand binding assays were utilised to characterise the properties of adenosine A1 receptors in the dorsal vagal complex (NTS, area postrema and dorsal motor nucleus of the vagus) of pup and adult normotensive (Wistar Kyoto, WKY) and hypertensive (spontaneously hypertensive, SHR) rats. Saturation binding indicated that the affinity (KD) of [3H]DPCPX, and the binding site density (Bmax) were not different between the adult WKY and SHR, although the pup SHR had a lower KD value than the pup WKY rat. Competition binding assays revealed complex differences between the two rat strains; however, with respect to hypertension, the affinity of the selective adenosine A1 agonist, cyclohexyladenosine (CHA), was markedly reduced in the membranes from SHR (Ki approximately 93 nM) compared to WKY (approximately 6 nM). Such an observation is consistent with the attenuated responses of SHRs to intra-NTS injections of adenosine.

摘要

本研究采用[3H]DPCPX体外受体放射自显影技术,以观察大鼠结状神经节上腺苷A1受体的存在情况,该神经节包含投射至孤束核(NTS)的迷走传入神经元的胞体。此外,单侧迷走神经结扎导致结扎部位附近[3H]DPCPX结合增加,表明腺苷A1受体沿大鼠迷走神经进行轴浆运输。利用放射性配体结合试验对幼鼠和成年正常血压(Wistar Kyoto,WKY)及高血压(自发性高血压,SHR)大鼠迷走神经背侧复合体(NTS、最后区和迷走神经背运动核)中腺苷A1受体的特性进行了表征。饱和结合表明,成年WKY和SHR之间[3H]DPCPX的亲和力(KD)和结合位点密度(Bmax)没有差异,尽管幼龄SHR的KD值低于幼龄WKY大鼠。竞争结合试验揭示了两种大鼠品系之间存在复杂差异;然而,就高血压而言,与WKY(约6 nM)相比,选择性腺苷A1激动剂环己基腺苷(CHA)在SHR膜中的亲和力显著降低(Ki约为93 nM)。这一观察结果与SHR对NTS内注射腺苷的反应减弱一致。

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