Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom.
Pharmacol Rev. 2010 Dec;62(4):565-78. doi: 10.1124/pr.110.002774.
Kisspeptins are members of the Arg-Phe amide family of peptides, which have been identified as endogenous ligands for a G-protein-coupled receptor encoded by a gene originally called GPR54 (also known as AXOR12 or hOT7T175). After this pairing, the gene has been renamed KISS1R. The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification recommends that the official name for the receptor is the kisspeptin receptor to follow the convention of naming the receptor protein after the endogenous ligand. The endogenous ligand was initially called metastin, after its role as a metastasis suppressor, and is now referred to as kisspeptin-54 (KP-54), a C-terminally amidated 54-amino acid peptide cleaved from the 145-amino acid gene product. Shorter C-terminal cleavage fragments [KP-14, KP-13 and KP-10 (the smallest active fragment)] are also biologically active. Both receptor and peptide are widely expressed in human, rat, and mouse; the receptor sequence shares more than 80% homology in these species. Activation of the kisspeptin receptor by kisspeptin is via coupling to G(q/11) and the phospholipase C pathway, causing Ca(2+) mobilization. Mutations in the KISS1R gene result in hypogonadotropic hypogonadotropism, and targeted disruption of Kiss1r in mice reproduces this phenotype, which led to the discovery of the remarkable ability of the kisspeptin receptor to act as a molecular switch for puberty. In addition to regulating the reproductive axis, the kisspeptin receptor is also implicated in cancer, placentation, diabetes, and the cardiovascular system.
Kisspeptins 是 Arg-Phe 酰胺肽家族的成员，已被鉴定为最初称为 GPR54（也称为 AXOR12 或 hOT7T175）的基因编码的 G 蛋白偶联受体的内源性配体。在这种配对之后，该基因已被重新命名为 KISS1R。国际基础与临床药理学联合会受体命名和药物分类委员会建议，该受体的正式名称为 kisspeptin 受体，遵循以内源性配体命名受体蛋白的惯例。内源性配体最初被称为 metastin，因其作为转移抑制剂的作用，现在被称为 kisspeptin-54 (KP-54)，这是一种从 145 个氨基酸基因产物中切割的 C 端酰胺化 54 个氨基酸肽。较短的 C 端切割片段[KP-14、KP-13 和 KP-10（最小的活性片段）]也具有生物活性。受体和肽在人和大鼠、小鼠中广泛表达；这些物种中的受体序列具有超过 80%的同源性。Kisspeptin 通过与 G(q/11)和磷脂酶 C 途径偶联激活 kisspeptin 受体，导致 Ca(2+)动员。KISS1R 基因的突变导致促性腺激素释放激素缺乏性性腺功能减退症，而 Kiss1r 在小鼠中的靶向缺失重现了这种表型，这导致发现 kisspeptin 受体作为青春期的分子开关的惊人能力。除了调节生殖轴外，kisspeptin 受体还与癌症、胎盘形成、糖尿病和心血管系统有关。
