Sakura N, Kurosawa K, Hashimoto T
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Chem Pharm Bull (Tokyo). 2000 Aug;48(8):1166-70. doi: 10.1248/cpb.48.1166.
To examine the role of both Arg residues at positions 5 and 7 of dog neuromedin U-8 (d-NMU-8; pGlu1-Phe-Leu-Phe-Arg5-Pro-Arg7-Asn8-NH2) for smooth muscle contractile activity on isolated chicken crop, d-NMU-8 analogs were synthesized where either Arg residue was systematically replaced by various amino acids [X: Ala, Thr, Glu, Gln, Lys, Orn, His, citrulline (Cit) or homoarginine (Har)]. All [X5]-d-NMU-8, except for [Glu5]- and [Des-Arg5]-d-NMU-8, were full agonists, although their affinities to NMU receptors were decreased. No [X7]-d-NMU-8 showed contractile activity even at concentrations of 10(-5) mol/l, except for [Har7]-d-NMU-8, which retained weak biological activity. These analogs had no antagonistic activity against porcine neuromedin U-8 (p-NMU-8). The results revealed that Arg7 of d-NMU-8 is indispensable for receptor binding and activation to induce smooth muscle contraction, and the guanidino group of the side chain at position 7, but not at position 5, is strictly recognized by NMU receptors in the chicken crop.
为了研究犬神经介素U-8（d-NMU-8；pGlu1-Phe-Leu-Phe-Arg5-Pro-Arg7-Asn8-NH2）第5位和第7位的精氨酸（Arg）残基对离体鸡嗉囊平滑肌收缩活性的作用，合成了d-NMU-8类似物，其中任一Arg残基被各种氨基酸[X：丙氨酸、苏氨酸、谷氨酸、谷氨酰胺、赖氨酸、鸟氨酸、组氨酸、瓜氨酸（Cit）或高精氨酸（Har）]系统取代。除了[Glu5]-d-NMU-8和[去-Arg5]-d-NMU-8外，所有[X5]-d-NMU-8都是完全激动剂，尽管它们对NMU受体的亲和力有所降低。除保留弱生物活性的[Har7]-d-NMU-8外，即使在10(-5)mol/l的浓度下，也没有[X7]-d-NMU-8表现出收缩活性。这些类似物对猪神经介素U-8（p-NMU-8）没有拮抗活性。结果表明，d-NMU-8的Arg7对于受体结合和激活以诱导平滑肌收缩是必不可少的，并且第7位而非第5位侧链的胍基被鸡嗉囊中的NMU受体严格识别。
