生长素释放肽的发现、发展及展望

生长素释放肽（Growth hormone-releasing peptides,GHRP)于70年代末、80年代初依据蛋氨酸－亮氨酸脑啡肽（met-enkephalin）的结构首次合成。以后又合成了数种类型的GHRP，其结构已远不同于met-enkephalin的结构。但均可强烈刺激生长素（growth hormone,GH）分泌。由于1982年下丘脑生长素释放激素的发现，GHRP研究在80年代进展不大。在90年代，由于制药界的努力和驱动，GHRP研究进展较快，非肽类生长素释放刺激剂（non-peptide GH secretagogues）于1994年首次合成，第一个GHRP受体也于1996年首次克隆成功。1999年从胃内分泌细胞首次发现可能的内源性GHRP,命名为ghrelin。Glrelin可激动GHRP受体并刺激GH分泌。最近几年，GHRP对生长素轴以外的外周组织的作用有诸多报道。GHRP的这些外周作用包括对心血管功能、摄食、脂肪细胞分化、胃酸分泌和胃肠运动的调节等。

Discovery, progess and future of growth hormone releasing peptides

Growth hormone releasing peptides (GHRP) was synthesised in late 70s based initially on the structure of met enkephalin. Several forms of GHRP were then developed and were structurally far from that of met enkephalin but strongly stimulate the GH release. Since the discovery of hypothalamic GH releasing hormone in 1982, research in GHRP had not experiencing a rapid progress until 90s due largely to the involvement of pharmaceutical research and development efforts. Non peptide GH secretagogues were synthesised in 1994 and first GHRP receptor was cloned in 1996. Possible endogenous GHRP, ghrelin, was discovered in 1999 from stomach endocrine cells. Ghrelin activated GHRP receptor and stimulate GH secretion. In recent years, GHRP effects on peripheral tissues outside the GH axis have been frequently reported. Those peripheral effects include the regulation of cardiovascular function, feeding, adipocytes proliferation, gastric acid secretion and gastro intestinal wriggle.