Yokoo H, Nakahara T, Matsumoto T, Inanaga K, Uchimura H
Peptides. 1987 Jan-Feb;8(1):49-53. doi: 10.1016/0196-9781(87)90164-1.
Tyrosine hydroxylase (TH) was assayed in eight regions of rat brain following repeated treatment with a TRH analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide). Repeated DN-1417 treatment (20 mg/kg/day, IP) for 7 days increased TH activity in the ventral tegmental area and decreased in the prefrontal cortex polar, medial and lateral fields and olfactory tubercles. No significant change in TH activity was found in the nucleus accumbens, striatum and substantia nigra. Kinetic analysis showed that the increased TH activity in the ventral tegmental area was due to an increase in Vmax, but not a change in the apparent Km of TH for a cofactor, 6-methyl-tetrahydropteridine. When TH was assayed at a suboptimal pH and in the presence of a subsaturating cofactor, the striatal TH was activated significantly after DN-1417. In the prefrontal cortex medial field, nucleus accumbens and olfactory tubercles, TH activity assayed under the suboptimal condition was not modified by DN-1417 treatment. These results suggest an intimate involvement of central dopaminergic systems in the actions of DN-1417.
在用促甲状腺激素释放激素类似物DN - 1417（γ-丁内酯-γ-羰基-组氨酰-脯氨酰胺）反复处理后，对大鼠脑的八个区域进行了酪氨酸羟化酶（TH）测定。反复给予DN - 1417（20毫克/千克/天，腹腔注射）7天，可使腹侧被盖区的TH活性增加，而前额叶皮质极区、内侧和外侧区以及嗅结节中的TH活性降低。伏隔核、纹状体和黑质中的TH活性未发现显著变化。动力学分析表明，腹侧被盖区TH活性的增加是由于Vmax增加，而不是TH对辅因子6 - 甲基-四氢蝶呤的表观Km发生变化。当在次优pH值和存在亚饱和辅因子的情况下测定TH时，DN - 1417处理后纹状体TH被显著激活。在前额叶皮质内侧区、伏隔核和嗅结节中，在次优条件下测定的TH活性未因DN - 1417处理而改变。这些结果表明中枢多巴胺能系统密切参与了DN - 1417的作用。
