Shimamura M, Kawamuki K, Hazato T
J Neurochem. 1987 Aug;49(2):536-40. doi: 10.1111/j.1471-4159.1987.tb02897.x.
Various angiotensins, bradykinins, and related peptides were examined for their inhibitory activity against several enkephalin-degrading enzymes, including an aminopeptidase and a dipeptidyl aminopeptidase, purified from a membrane-bound fraction of monkey brain, and an endopeptidase, purified from the rabbit kidney membrane fraction. Angiotensin derivatives having a basic or neutral amino acid at the N-terminus showed strong inhibition of the aminopeptidase. Dipeptidyl aminopeptidase was inhibited by angiotensins II and III and their derivatives, whereas the endopeptidase was inhibited by angiotensin I and its derivatives. The most potent inhibitor of aminopeptidase and dipeptidyl aminopeptidase was angiotensin III, which completely inhibited the degradation of enkephalin by enzymes in monkey brain or human CSF. The Ki values for angiotensin III against aminopeptidase, dipeptidyl aminopeptidase, endopeptidase, and angiotensin-converting enzyme, which degraded enkephalin, were 0.66 X 10(-6), 1.03 X 10(-6), 2.3 X 10(-4), and 1.65 X 10(-6) M, respectively. Angiotensin III potentiated the analgesic activity of Met-enkephalin after intracerebroventricular coadministration to mice in the hot plate test. Angiotensin III itself also displayed analgesic activity in that test. These actions were blocked by the specific opiate antagonist naloxone.
研究了多种血管紧张素、缓激肽及相关肽对几种脑啡肽降解酶的抑制活性，这些酶包括从猴脑的膜结合部分纯化得到的一种氨肽酶和一种二肽基氨肽酶，以及从兔肾膜部分纯化得到的一种内肽酶。在N端具有碱性或中性氨基酸的血管紧张素衍生物对氨肽酶表现出强烈的抑制作用。二肽基氨肽酶受到血管紧张素II和III及其衍生物的抑制，而内肽酶则受到血管紧张素I及其衍生物的抑制。氨肽酶和二肽基氨肽酶最有效的抑制剂是血管紧张素III，它能完全抑制猴脑或人脑脊液中酶对脑啡肽的降解。血管紧张素III对氨肽酶、二肽基氨肽酶、内肽酶以及能降解脑啡肽的血管紧张素转换酶的Ki值分别为0.66×10⁻⁶、1.03×10⁻⁶、2.3×10⁻⁴和1.65×10⁻⁶M。在热板试验中，向小鼠脑室内共同给药后，血管紧张素III增强了甲硫氨酸脑啡肽的镇痛活性。血管紧张素III本身在该试验中也表现出镇痛活性。这些作用被特异性阿片拮抗剂纳洛酮阻断。
