Garzón J, Sánchez-Blázquez P
Neuropharmacology Unit, Cajal Institute, C.S.I.C., Madrid, Spain.
Life Sci. 1991;48(14):1417-27. doi: 10.1016/0024-3205(91)90439-i.
alpha N-acetyl human beta-endorphin-(1-31) injected icv to mice antagonized the analgesic activity of beta-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of alpha N-acetyl beta-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of alpha N-acetyl human beta-endorphin-(1-31) was partially retained by the shorter peptide alpha N-acetyl human beta-endorphin-(1-27) and to a lesser extent by beta-endorphin-(1-27), beta-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated beta-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM [125I]-Tyr27 human beta-endorphin-(1-31) specific binding, the first step (20 to 30% of the binding) was abolished with an apparent IC50 of 0.35 nM, and the rest with an IC50 of 200 nM. It is suggested that alpha N-acetyl beta-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins Gi/Go.
向小鼠脑室内注射α-N-乙酰基人β-内啡肽-（1-31）可拮抗β-内啡肽-（1-31）和吗啡的镇痛活性，而这种处理可增强DADLE和DAGO诱发的镇痛作用。α-N-乙酰基β-内啡肽-（1-31）的调节活性在极低剂量（飞摩尔）时就表现出来，即使剂量增加100,000倍，其最大值仍持续存在。单剂量的乙酰化神经肽的调节作用持续24小时。较短的肽α-N-乙酰基人β-内啡肽-（1-27）部分保留了α-N-乙酰基人β-内啡肽-（1-31）的活性，β-内啡肽-（1-27）的保留程度较小，β-内啡肽-（1-31）对阿片类镇痛缺乏这种调节活性。乙酰化的β-内啡肽-（1-31）与5 pM [125I]-酪氨酸27人β-内啡肽-（1-31）特异性结合时呈现双相曲线，第一步（结合的20%至30%）在表观IC50为0.35 nM时被消除，其余部分在IC50为200 nM时被消除。有人提出，α-N-乙酰基β-内啡肽-（1-31）通过作用于与阿片受体功能偶联的特定底物（可能是鸟嘌呤核苷酸结合调节蛋白Gi/Go）来改变阿片类镇痛药的效率。
