Search for novel neuropeptides using orphan receptor expressing cell systems.

生长激素促分泌素（GHS）是一种合成的小分子，通过G蛋白偶联受体GHS-R刺激垂体释放生长激素（GH）。最近克隆的GHS-R强烈建议存在的受体的内源性配体，和生长激素调节的机制不同，由下丘脑生长激素释放激素（GHRH）。我们在这里报告的纯化和鉴定在大鼠胃中的一个新的内源性GHS-R特异性配体。纯化的配体是由28个氨基酸组成的新型肽，其中Ser-3残基被正辛酰化。酰基肽在体内和体外特异性释放GH。Ser-3的O-正辛酰化对活性至关重要。我们将释放GH的肽命名为“GHRE IN”（“ghre”是单词“grow”的原始印欧语词根）。人生长激素释放肽与大鼠生长激素释放肽高度同源，除了只有两个氨基酸被替换。人和大鼠体内均存在ghrelin，提示垂体GH的释放不仅受下丘脑GHRH的调节，而且受新发现的ghrelin的调节。

Small synthetic molecules termed growth hormone secretagogues (GHSs) act through an orphan G-protein coupled receptor, GHS-R, to stimulate growth hormone (GH) release from pituitary. Recent cloning of GHS-R strongly suggests the presence of an endogenous ligand for the receptor, and of a mechanism for GH-regulation distinct from that by hypothalamic growth hormone-releasing hormone (GHRH). We report here purification and identification in rat stomach of a new endogenous ligand specific for GHS-R. The purified ligand is a novel peptide consisting of 28 amino acids, in which the Ser-3 residue is n-octanoylated. The acylas peptide specifically releases GH in vivo as well as in vitro. O-n-octanoylation at Ser-3 is essential to the activity. We designate the GH-releasing peptide "GHRELIN" ("ghre" is the Proto-Indo-European root of the word "grow"). Human ghrelin is highly homologous to rat ghrelin except that only two amino acids are replaced. Occurrence of ghrelin in both rat and human indicates that GH release from pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin newly identified.