Guglietta A, Irons B J, Lazarus L H, de Castiglione R, Melchiorri P
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental and Health Sciences, Research Triangle Park, NC 27709.
Methods Find Exp Clin Pharmacol. 1989 Nov;11(11):663-70.
The effect of centrally administered dermorphin and a series of dimeric dermorphin analogs on gastric acid secretion was studied in pylorusligated rats. Dimeric dermorphin analogs consist of identical peptide chains either directly linked with a dihydride bond or a polyethyleneamine bridge at their carboxy termini. At a dose of 0.5 nmol dermorphin, and the dimeric analogs di-[D-Arg2,Sar4]-tetra-DM2, di-penta-DM0, di-[Sar4]-penta-DM0, di-[D-Arg2,Sar4]-penta-DM0, di-[D-Ala4]-penta-DM0 and di-DM0, and di-DM0, inhibited gastric acid output in a statistically significant manner (P less than 0.05). Furthermore, the binding characteristics of these peptides for the mu-type opioid receptor were analyzed using a brain synaptosomal fraction. Dermorphin and several dimeric dermorphin peptides bound to the mu-receptor: di-penta-DM0, di-[Sar4]-penta-DM0, di-penta-DM2 and di-DM0, had 3-to 5-fold greater affinity for the mu-receptor than the specific mu-agonist DAGO. These data indicate that a correlation exists between the central mediated gastric inhibitory effect of DM and several dimeric analogs and their affinity for the mu-type opioid receptor in rat brain.
在幽门结扎的大鼠中研究了中枢给予的德莫啡肽及一系列二聚体德莫啡肽类似物对胃酸分泌的影响。二聚体德莫啡肽类似物由相同的肽链组成，这些肽链在其羧基末端通过二硫键或聚乙烯胺桥直接相连。在0.5 nmol德莫啡肽以及二聚体类似物二 - [D - Arg2，Sar4] - 四 - DM2、二 - 五 - DM0、二 - [Sar4] - 五 - DM0、二 - [D - Arg2，Sar4] - 五 - DM0、二 - [D - Ala4] - 五 - DM0和二 - DM0的剂量下，均能以统计学显著方式抑制胃酸分泌（P小于0.05）。此外，使用脑突触体部分分析了这些肽与μ型阿片受体的结合特性。德莫啡肽和几种二聚体德莫啡肽与μ受体结合：二 - 五 - DM0、二 - [Sar4] - 五 - DM0、二 - 五 - DM2和二 - DM0对μ受体的亲和力比特异性μ激动剂DAGO高3至5倍。这些数据表明，德莫啡肽和几种二聚体类似物的中枢介导的胃抑制作用与其对大鼠脑内μ型阿片受体的亲和力之间存在相关性。
