Schiöth H B, Muceniece R, Mutulis F, Bouifrouri A A, Mutule I, Wikberg J E
Department of Pharmaceutical Pharmacology, Uppsala University, Uppsala, Sweden.
Neuropeptides. 1999 Jun;33(3):191-6. doi: 10.1054/npep.1999.0760.
SHU9119 and HS014 are cyclic MSH analogues which are widely used to elucidate the physiology behind the various effects of the MSH peptides and their receptors. We carefully compared the potency of SHU9119 and HS014 in cells expressing the MC receptor clones. We found that both the peptides are partial agonists for the MC1 and MC5 receptors while they are potent antagonists for the MC3 and MC4 receptors. In agreement with earlier binding data, we found that SHU9119 has equal potency for the MC3 and MC4 receptor whereas HS014 has at least 10-fold higher potency for the MC4 receptor than the MC3 receptor in cAMP assay. Moreover, we synthesized analogues of HS014 where the C-terminal was truncated. We found that this C-terminal fragment of HS014, in particular the Lys(14), has a major influence on the affinity for the MC4 receptor without any particular influence on the affinity for the other MC receptors.
SHU9119和HS014是环状促黑素（MSH）类似物，被广泛用于阐明MSH肽及其受体的各种效应背后的生理学机制。我们仔细比较了SHU9119和HS014在表达促黑素细胞激素（MC）受体克隆的细胞中的效力。我们发现，这两种肽对MC1和MC5受体都是部分激动剂，而对MC3和MC4受体则是强效拮抗剂。与早期的结合数据一致，我们发现在环磷酸腺苷（cAMP）测定中，SHU9119对MC3和MC4受体的效力相同，而HS014对MC4受体的效力比对MC3受体至少高10倍。此外，我们合成了HS014的类似物，其中C端被截短。我们发现，HS014的这个C端片段，特别是赖氨酸（14），对MC4受体的亲和力有重大影响，而对其他MC受体的亲和力没有任何特别影响。
