REDUCED D2 DOPAMINE AND MUSCARINIC CHOLINERGIC RECEPTOR DENSITIES IN CAUDATE SPECIMENS FROM FLUCTUATING PARKINSONIAN-PATIENTS
REDUCED D2 DOPAMINE AND MUSCARINIC CHOLINERGIC RECEPTOR DENSITIES IN CAUDATE SPECIMENS FROM FLUCTUATING PARKINSONIAN-PATIENTS
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DOI：
10.1002/ana.410300210
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发表时间：
1991-08-01
影响因子：
11.2
通讯作者：
CARMICHAEL, SW
中科院分区：
文献类型：
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作者：
AHLSKOG, JE;RICHELSON, E;CARMICHAEL, SW
用氢3（H-3）标记的螺哌隆和二苯羟乙酸3-奎宁环酯（QNB）在脑移植时从8名存活的帕金森病患者获得的尾状体组织中测定结合。这是一个临床上同质的患者组：所有患者对左旋多巴仍主要有反应，尽管有继发于临床波动（短期反应）和药物诱导的运动障碍的明显残疾;所有患者均接受了大量剂量的左旋多巴，8例患者中有6例额外接受了溴隐亭或培高利特。多巴胺D2受体的结合密度，测定[H-3]螺哌隆结合，减少在这组患者相比，尾状体标本尸检对照组。这一发现可能反映了药物诱导的受体下调。与毒蕈碱胆碱能受体发生平行变化;与尸检对照值相比，[H-3]QNB结合显著降低。这种毒蕈碱受体的减少可能是由于已知含有毒蕈碱受体的黑质纹状体末端的丢失。或者，毒蕈碱受体可能已下调增加皮质纹状体神经递质输入胆碱能细胞，推断是存在的基础上突出的左旋多巴诱导的运动障碍。最后，受体缺陷也可能是更广泛的退行性脑疾病的反映，尽管左旋多巴难治性症状在这些患者中通常不明显。
Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (H-3), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was a clinically homogeneous group of patients: All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [H-3]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This finding may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [H-3]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have also been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.