Yamada S, Isogai M, Okudaira H, Hayashi E
Brain Res. 1983 Jun 6;268(2):315-20. doi: 10.1016/0006-8993(83)90498-5.
The specific [3H]QNB binding and high-affinity uptake of [14C]choline in 8 brain regions (cerebral cortex, hippocampus, hypothalamus, thalamus, striatum, midbrain, cerebellum and brainstem) after repeated administration of DFP and atropine to guinea-pigs were simultaneously measured. Following repeated DFP administration, AChE was markedly depressed in each brain region. In these animals, there was a significant decrease in specific [3H]QNB binding in the cerebral cortex, hippocampus and striatum, whereas the [3H]QNB binding in the rest of brain regions was unchanged. Scatchard analysis revealed a 36% decrease in the Bmax value for the striatal [3H]QNB binding without a change in the Kd value, suggesting a change in the receptor density. In contrast, repeated atropine administration produced a significant enhancement in the [3H]QNB binding only in the hippocampus and striatum. The Bmax value in the striatum increased by 21% without a change in the Kd value. In addition to the receptor alteration, high affinity uptake of [14C]choline in the hippocampus and striatum was significantly decreased by DFP treatment, while that in the striatum increased by atropine treatment. Thus the present study has demonstrated that a prolonged activation and blockade of central muscarinic receptors resulted in specific adaptation in both the receptor density and ACh availability at the synapses in the cerebral cortex, hippocampus and striatum.
在豚鼠反复给予二异丙基氟磷酸酯（DFP）和阿托品后，同时测量了8个脑区（大脑皮层、海马体、下丘脑、丘脑、纹状体、中脑、小脑和脑干）中特异性[3H]QNB结合以及[14C]胆碱的高亲和力摄取。反复给予DFP后，每个脑区的乙酰胆碱酯酶（AChE）均显著降低。在这些动物中，大脑皮层、海马体和纹状体中的特异性[3H]QNB结合显著减少，而其余脑区的[3H]QNB结合未发生变化。Scatchard分析显示，纹状体[3H]QNB结合的Bmax值降低了36%，而Kd值未改变，提示受体密度发生了变化。相比之下，反复给予阿托品仅使海马体和纹状体中的[3H]QNB结合显著增强。纹状体中的Bmax值增加了21%，而Kd值未改变。除了受体改变外，DFP处理使海马体和纹状体中[14C]胆碱的高亲和力摄取显著降低，而阿托品处理则使其增加。因此，本研究表明，中枢毒蕈碱受体的长期激活和阻断导致大脑皮层、海马体和纹状体突触处的受体密度和乙酰胆碱可用性发生特异性适应性变化。
