ABNORMALITY OF ALPHA-ADRENERGIC RECEPTORS IN THE FRONTAL CORTEX OF GEPR

GEPR 额叶皮层α-肾上腺素能受体异常

• 批准号: 4696426
• 负责人: F NICOLETTI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696426
• 关键词: brain mapping; congenital brain disorder; epilepsy; human tissue; inferior colliculus; inositol phosphates; neuropharmacology; norepinephrine; prazosin; radiotracer

We have found that the binding site of 3H-prazosin, a selective ligand for Alpha1-adrenergic recognition sites is significantly lower in the frontal cortex of the genetically epilepsy prone rats (GEPR), as compared with normal Sprague Dawley rats. Scratched analysis reveals a decrease in the Bmax of 3H-prazosin binding with no change int he apparent KD, suggesting that there are fewer Alpha1-adrenergic recognition sites in the frontal cortex of the GEPR. This abnormality is assocaited with a reduced capacity of norepinephrine (NE) to stimulate 3H-inositol-l-phosphate formation in frontal cortex slices prelabeled with 3H-inositol. No significant differences in 3H-prazosin binding as well as NE-stimulated 3H-inositol-l-phosphate formation have been observed in other brain regions including hippocampus, corpus striatum and inferior colluculus. These results indicate that a deficit in the X1-adrenergic receptor system in the frontal cortex may play a role in the seizure process in the GEPR.

我们发现了~3H-哌唑嗪的结合部位，它是一种选择性配体。 α1-肾上腺素能识别部位在额叶显著较低 遗传性癫痫易感大鼠(GEPR)大脑皮质与 正常SD大鼠。划痕分析显示， ~3H-哌唑嗪结合的最大结合数与表观Kd无变化，提示 额叶中的α1-肾上腺素能识别部位较少 GEPR的皮质。这种异常与容量降低有关 去甲肾上腺素(NE)刺激大鼠心肌细胞生成~3H-肌醇-L-磷酸 额叶皮质切片预先标记了~3H-肌醇。没有重大意义 ~3H-哌唑嗪结合与去甲肾上腺素刺激的差异 在其他脑区也观察到了~3H-肌醇-L-磷酸的形成 包括海马体、纹状体和下丘。这些 结果表明，X1-肾上腺素能受体系统存在缺陷。 额叶皮质可能在GEPR的癫痫发作过程中发挥作用。