Adenosine receptors and the nucleoside transporter in human brain vasculature.
Adenosine receptors and the nucleoside transporter in human brain vasculature.
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人脑脉管系统中的腺苷受体和核苷转运蛋白。
DOI：
10.1038/jcbfm.1988.5
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Harik,SI
中科院分区：
文献类型：
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作者：
Kalaria,RN;Harik,SI
有证据表明腺苷通过与脑细胞和血管上的特定受体相互作用来调节神经元和脑血管功能。腺苷和其他核苷也通过饱和的载体介导机制通过血脑屏障进行转运。采用直接配体结合的方法，我们研究了人脑微血管、脑脊膜、脉络膜丛和大脑皮层膜中的两种腺苷受体亚型a1和A2以及核苷转运体片段。使用了以下特定的氚化配体：环己基腺苷（CHA）用于a1受体；a2受体的5'- n -乙基羧酰胺腺苷（NECA）；硝基苄基硫代肌苷（NBMPR）和双嘧达莫（DPY）作为核苷转运体。我们发现，与脑膜相比，大脑微血管、脑脊膜和脉络膜丛的a1受体很少（如果有的话），而脑膜的a1受体密度要高10 - 20倍。在大脑微血管、脑脊膜和脉络膜丛中，NECA与a2受体的特异性高亲和力结合是饱和的，相当于大脑皮质膜。高亲和NECA与血管制剂结合的bmaxa和kd2分别为~ 1.3 pmol/mg蛋白和~ 250 nM，这与我们之前在大鼠和猪中的发现相似。NBMPR和结合也是饱和的，与一类高亲和力结合位点一致。核苷转运体在大脑微血管中的密度是大脑皮层、脑脊膜血管和脉络膜丛的4倍。这些结果表明，人类大脑微血管有A2受体，而不是A1受体，并且腺苷转运体部分特别丰富。
Evidence suggests that adenosine modulates neuronal and cerebral vascular functions by interacting with specific receptors on brain cells and blood vessels. Adenosine and other nucleosides are also transported across the blood-brain barrier via a saturable, carrier-mediated mechanism. Using direct ligand binding methods, we studied the two adenosine receptor subtypes, A1and A2, and the nucleoside transporter moiety in human brain microvessels, pial vessels, choroid plexus, and cerebral cortex membranes. The following specific tritiated ligands were used: cyclohexyladenosine (CHA) for A1receptors; 5'-N-ethylcarboxamide adenosine (NECA) for A2receptors; nitrobenzylthioinosine (NBMPR) and dipyridamole (DPY) for nucleoside transporters. We find that cerebral microvessels, pial vessels, and choroid plexus have few, if any, A1receptors, in contradistinction to cerebral membranes, which have a 10–20-fold higher density of A1receptor sites. Specific high-affinity NECA binding to A2receptors in cerebral microvessels, pial vessels, and choroid plexus was saturable and was equivalent to that of cerebral cortical membranes. TheBmaxandKdof the high-affinity NECA binding to vessel preparations were ∼1.3 pmol/mg protein and ∼250 nM, respectively, which is similar to our previous findings in the rat and pig. NBMPR and binding were also saturable and were consistent with a single class of high-affinity binding sites. The density of nucleoside transporters was ∼four-fold higher in cerebral microvessels than in cerebral cortex, pial vessels, and choroid plexus. These results suggest that human cerebral microvessels have A2, but not A1, receptors and are particularly enriched with the adenosine transporter moiety.