CHARACTERIZATION OF N-[H-3]METHYLCARBAMYLCHOLINE BINDING-SITES AND EFFECT OF N-METHYLCARBAMYLCHOLINE ON ACETYLCHOLINE-RELEASE IN RAT-BRAIN
CHARACTERIZATION OF N-[H-3]METHYLCARBAMYLCHOLINE BINDING-SITES AND EFFECT OF N-METHYLCARBAMYLCHOLINE ON ACETYLCHOLINE-RELEASE IN RAT-BRAIN
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DOI：
10.1111/j.1471-4159.1988.tb04869.x
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发表时间：
1988-07-01
影响因子：
4.7
通讯作者：
QUIRION, R
中科院分区：
文献类型：
--
作者：
ARAUJO, DM;LAPCHAK, PA;QUIRION, R
本实验表明，N-[~ 3 H]-甲基氨甲酰胆碱（[~ 3 H]MCC）与大鼠海马、额叶皮质和纹状体特异性结合，并具有高亲和力。结合位点的最大密度在额叶皮层最高，在海马最低。[3 H]MCC结合被烟碱激动剂而非毒蕈碱激动剂和烟碱拮抗剂二氢-β-腺苷酸有效抑制。在研究的所有三个大脑区域中，赤藓红定。未标记MCC对大鼠脑片乙酰胆碱（ACh）释放的影响进行了测试：该药物显着增强海马和额叶皮质片的自发ACh释放，但不从纹状体片。MCC增加大鼠海马和额叶皮质ACh释放的这种作用被烟碱拮抗剂二氢-β-赤藓定和d-筒箭毒碱，但不被α-银环蛇毒素或毒蕈碱拮抗剂阿托品。MCC诱导的海马和额叶皮质脑片乙酰胆碱自发释放的增加不受河豚毒素的影响。结果提示，MCC可能通过直接激活胆碱能终末突触前烟碱受体而改变大鼠脑内胆碱能传递。这种ACh释放的改变在海马和额叶皮质中是明显的，而在纹状体中则不明显，这表明在大鼠脑中烟碱受体对ACh的调节可能具有区域特异性。
The present experiments show that N-[3H]-methylcarbamylcholine ([3H]MCC) binds specifically and with high affinity to rat hippocampus, frontal cortex, and striatum. The highest maximal density of binding sites was apparent in frontal cortex and the lowest in hippocampus. [3H]MCC binding was potently inhibited by nicotinic, but not muscarinic, agonists and by the nicotinic antagonist dihydro-.beta.-erythroidine in all three brain regions studied. The effect of unlabeled MCC on acetylcholine (ACh) release from slices of rat brain was tested: the drug significantly enhanced spontaneous ACh release from slices of hippocampus and frontal cortex, but not from striatal slices. This effect of MCC to increase ACh release from rat hippocampus and frontal cortex was antagonized by the nicotinic antagonists dihydro-.beta.-erythroidine and d-tubocurarine, but not by .alpha.-bungarotoxin or by the muscarinic antagonist atropine. The MCC-induced increase in spontaneous ACh release from hippocampal and frontal cortical slices was not affected by tetrodotoxin. The results suggest that MCC might alter cholinergic transmission in rat brain by a direct activation of presynaptic nicotinic receptors on the cholinergic terminals. That this alteration of ACh release is apparent in hippocampus and frontal cortex, but not in striatum, suggests that there may be a regional specificity in the regulation of ACh by nicotinic receptors in rat brain.