Baertschi A J, Zingg H H, Dreifuss J J
Brain Res. 1981 Sep 7;220(1):107-19. doi: 10.1016/0006-8993(81)90214-6.
To test the hypothesis that enkephalins, substance P, bradykinin and angiotensin II could act as neurohumoral modulators of hypothalamic function, these peptides (0.01-20 microgram) were injected into the general circulation of anesthetized rats, and changes in hypothalamo-neurohypophysial activity were determined by continuously monitoring the amplitude of antidromic compound action potentials (CAP) in the hypothalamo-hypophysial tract. A decrease of CAP amplitude was taken to indicate an increase of orthodromic impulse traffic. All peptides elicited a CAP decrease. On a molar basis when injected i.v., the enkephalin analog FK 33-824 was the most effective substance, followed by substance P, Leu-enkephalin and angiotensin II. Enkephalins and substance P injected through the internal carotid artery, were 2-5 times more effective than when injected i.v., whereas bradykinin was most effective when it reached the brain through a vertebral route. Angiotensin II produced the same CAP decrease irrespective of the route of administration and, in contradistinction to the other peptides, its effect was not abolished by stalk section. Tachyphylaxis and reversibility with naloxone was observed only for the enkephalins. The data suggest that sites of action are the hypothalamus for enkephalins and substance P, the neurohypophysis for angiotensin II, and the hindbrain for bradykinin.
为了验证脑啡肽、P物质、缓激肽和血管紧张素II可作为下丘脑功能的神经体液调节剂这一假说，将这些肽（0.01 - 20微克）注入麻醉大鼠的体循环中，并通过连续监测下丘脑 - 垂体束中逆行复合动作电位（CAP）的幅度来测定下丘脑 - 神经垂体活动的变化。CAP幅度降低被视为顺行冲动传递增加的指标。所有肽均引起CAP降低。静脉注射时，按摩尔计算，脑啡肽类似物FK 33 - 824是最有效的物质，其次是P物质、亮氨酸脑啡肽和血管紧张素II。通过颈内动脉注射脑啡肽和P物质时，其效果比静脉注射时强2 - 5倍，而缓激肽经椎动脉途径进入脑时效果最佳。无论给药途径如何，血管紧张素II都能产生相同程度的CAP降低，与其他肽不同的是，其作用不会因切断垂体柄而消除。仅脑啡肽观察到快速耐受性和纳洛酮可逆性。数据表明，脑啡肽和P物质的作用部位是下丘脑，血管紧张素II的作用部位是神经垂体，缓激肽的作用部位是后脑。
