Receptor constants for endomorphin-1 and endomprphin-1-ol indicate differences in efficacy and receptor occupancy
Receptor constants for endomorphin-1 and endomprphin-1-ol indicate differences in efficacy and receptor occupancy
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DOI：
10.1016/s0014-2999(01)01014-7
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发表时间：
2001-06-01
影响因子：
5
通讯作者：
Rónai, AZ
中科院分区：
文献类型：
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作者：
Al-Khrasani, M;Orosz, G;Rónai, AZ
含有C-末端醇（-醇）功能的内吗啡肽衍生物的阿片样物质的性质进行了比较，在离体器官（豚鼠回肠和小鼠输精管的纵向肌条）的母体酰胺化化合物。对于μ-阿片样物质受体选择性激动剂合成肽（D-Ala（2），MePhe（4），Gly（5）-醇）-脑啡肽（DAMGO）及其Gly（5）-NH 2同源物（DAMGA）也产生了类似的数据。内吗啡肽-1-醇（Tyr-Pro-Trp-Phe-ol）在小鼠输精管和豚鼠回肠中的IC 50分别为80.6 nM和61.2 nM;内吗啡肽-2-醇（Tyr-Pro-Phe-Phe-ol）的相应值分别为49.6和48.2 nM，DAMGO分别为59.8和29.2 nM。如纳洛酮的拮抗作用所示，激动剂作用仅在两个器官中的μ阿片受体上发挥。的-醇衍生物是轻微的（2.3-4.3倍）比母体酰胺在生物测定中的效力较低：所有的肽，显然，完整的制剂中的完全激动剂的性质。为了揭示所研究的肽中潜在的部分激动剂性质，我们用5 × 10（-7）M β-funalcidamine部分灭活小鼠输精管中的μ-阿片受体库。计算的受体常数表明内吗啡肽-1的“高亲和力、低内在功效”特征（即潜在的部分激动剂性质）、内吗啡肽-1-醇的中间特征和DAMGA和DAMGO的完全激动作用。显然，在部分失活后，内吗啡肽-1（42.8%）比-醇同源物（14.0%）、DAMGO（20.2%）和DAMGA（14.1%）保持更高的受体分数。(C)出版社：Elsevier Science B. V.
The opioid properties of endomorphin derivatives containing a C-terminal alcoholic(-ol) function were compared to the parent amidated compounds in isolated organs (longitudinal muscle strip of guinea-pig ileum and mouse vas deferens). Similar data were also generated for the mu -opioid receptor selective agonist synthetic peptide (D-Ala(2), MePhe(4), Gly(5)-ol)-enkephalin (DAMGO) and its Gly(5)-NH2 congener (DAMGA). Endomorphin-1-ol (Tyr-Pro-Trp-Phe-ol) had an IC50 of 80.6 nM in mouse vas deferens and 61.2 nM in guinea-pig ileum; the corresponding values for endomorphin-2-ol (Tyr-Pro-Phe-Phe-ol) were 49.6 and 48.2 nM, for DAMGO 59.8 and 29.2 nM, respectively. As it was indicated by the antagonism by naltrexone, the agonist actions were exerted exclusively at mu -opioid receptors in both organs. The -ol derivatives were slightly (2.3-4.3 times) less potent than the parent amides in the bioassays: all peptides had, apparently, full agonist properties in intact preparations. With the aim of revealing potential partial agonist properties among the investigated peptides, we partially inactivated the mu -opioid receptor pool in mouse vas deferens by 5 X 10(-7) M beta -funaltrexamine. The calculated receptor constants indicated a "high-affinity, low intrinsic efficacy" profile (i.e. a potential partial agonist property) for endomorphin-1, an intermediate character for endomorpin-1-ol and full agonism for DAMGA and DAMGO. Apparently, a higher receptor fraction remained accessible for endomorphin-1 (42.8%) than for the -ol congener (14.0%), DAMGO (20.2%) and DAMGA (14.1%) after partial inactivation. (C) 2001 Published by Elsevier Science B.V.