Improta G, Broccardo M
Institute of Pharmacology III, University La Sapienza, Rome, Italy.
Peptides. 1992 Nov-Dec;13(6):1123-6. doi: 10.1016/0196-9781(92)90017-w.
Pharmacological assays in isolated tissues and binding tests have recently shown that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2, isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin I and II, respectively, possess a higher affinity and selectivity for delta-opioid receptors than any other known natural compound. Since much evidence supports the role of spinal delta-opioid sites in producing antinociceptive effects, we investigated whether analgesia might be detected by direct spinal cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu-selective agonist, were compared at different postinjection times by means of the tail-flick test. The DADELT II produced a dose-related inhibition of the tail-flick response, which lasted 10-60 min depending on the dose and appeared to be of shorter duration than the analgesia produced in rats after intrathecal injection of dermorphin (20-120 min). The analgesic effect of infused or injected DADELT II was completely abolished by naltrindole, the highly selective delta antagonist. These results confirm the involvement of delta receptors in spinal analgesic activity in the rat.
最近在离体组织中进行的药理学试验和结合试验表明，从双色叶泡蛙皮肤提取物中分离出的两种肽，其序列为Tyr-D-Ala-Phe-Asp-（或Glu）-Val-Val-Gly-NH2，分别命名为[D-Ala2]强啡肽I和II，对δ-阿片受体的亲和力和选择性高于任何其他已知的天然化合物。由于有大量证据支持脊髓δ-阿片位点在产生抗伤害感受作用中的作用，我们研究了在大鼠中直接脊髓给药[D-Ala2]强啡肽II（DADELT II）是否能检测到镇痛作用。通过甩尾试验比较了鞘内注射DADELT II和强效μ选择性激动剂德莫啡肽在不同注射后时间的热抗伤害感受作用。DADELT II产生了与剂量相关的甩尾反应抑制，持续时间为10 - 60分钟，具体取决于剂量，且似乎比鞘内注射德莫啡肽后在大鼠中产生的镇痛作用持续时间短（20 - 120分钟）。注入或注射的DADELT II的镇痛作用被高选择性δ拮抗剂纳曲吲哚完全消除。这些结果证实了δ受体参与大鼠脊髓镇痛活性。
