Gacel G, Fournié-Zaluski M C, Fellion E, Roques B P
J Med Chem. 1981 Oct;24(10):1119-24. doi: 10.1021/jm00142a002.
In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors) of the short peptide Tyr-D-Ala-Gly-NH-CH(CH3)CH2CH(CH3)2 (6) is 2100 times lower (IC50 = 1220 nM) than that of the longer and more hydrophilic peptide Tyr-D-Ser-Gly-Phe-Leu-Thr (10) (IC50 = 0.58 nM). In contrast, the IC50 values of all the synthesized compounds on the guinea pig ileum assay (mu receptors) are in the same range (100-360 nM). Likewise, their analgesic activities in mice, measured on the hot-plate test after intracerebroventricular injection, are similar. Therefore, the dissociation between antinociceptive properties in mice and potencies on the mouse vas deferens unambiguously reflects a preferential implication of mu receptors in analgesia. The possible involvement of brain delta receptors in behavioral effects is discussed.
为了研究μ受体或δ受体在脑啡肽镇痛作用中的优先参与情况，合成了几种在外周器官中与这两种受体选择性相互作用的肽。短肽Tyr-D-Ala-Gly-NH-CH(CH3)CH2CH(CH3)2（6）对电刺激小鼠输精管（δ受体）的抑制效力（IC50 = 1220 nM）比更长且亲水性更强的肽Tyr-D-Ser-Gly-Phe-Leu-Thr（10）（IC50 = 0.58 nM）低2100倍。相反，所有合成化合物在豚鼠回肠试验（μ受体）中的IC50值处于相同范围（100 - 360 nM）。同样，它们在小鼠脑室内注射后通过热板试验测量的镇痛活性相似。因此，小鼠的抗伤害感受特性与对小鼠输精管的效力之间的解离明确反映了μ受体在镇痛中的优先作用。讨论了脑δ受体在行为效应中可能的参与情况。
