Search for novel hormones and neuropeptides

这项建议的主要目的是利用各种检测方法分离新的激素和神经肽，并表征这些肽的生理和生化特性。为此，我们首先建立了一个新的实验室，能够进行多肽的分离、结构测定、化学合成以及各种生理和药理研究，然后我们进行了分离研究和各种生理研究。本研究从中国林蛙(Rana Rugosa)的皮肤中分离并鉴定了1)新的抗菌肽Rugoins、A、B和C；2)从猪肠中分离到一种新的CCK释放肽；3)从脑膜细胞中分离到了胰岛素样生长因子(IGF)-II和IGF结合蛋白-2；4)从猪肠中分离到了新的胃动素相关肽。我们还发现：1)脑膜在垂体切除后血管加压素神经再生中起神经营养作用；2)生物素C末端延伸的胃动素可作为生物活性受体探针；3)分化诱导因子(DIF-1)升高胰腺AR42J细胞内钙浓度并诱导其凋亡；4)胰腺抑素抑制分泌剂诱导的单个大鼠胰岛细胞内游离钙浓度的升高；5)GLP-1以Na+依赖的方式使大鼠胰腺B细胞去极化；6)缓激肽升高胰腺腺泡AR42J细胞内钙浓度。

The principal aim of this proposal is to isolate novel hormones and neuropeptides using a variety of assay methods and to characterize physiological and biochemical properties of the peptides. Toward this goal, we first set up a new laboratory which is capable of carrying out peptide isolation, structural determination, chemical synthesis and various physiological and pharmacological studies, then, we carried out isolation studies and various physiological studies. In this study, we isolated and characterized that : 1)novel antimicrobial peptides, rugosins, A,B,and C from the skin of the frog, rana rugosa ; 2)a novel CCK-releasing peptide from porcine intestine ; 3)insulin-like growth factor (IGF)-II and IGF binding protein-2 from brain meningeal cells ; 4)novel motilin-related peptides from porcine intestine. We also found that : 1)meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy ; 2)biotinyl C-terminal-extended motilin can be used as a biologically active receptor probe ; 3)differentiation-inducing factor (DIF-1) raises intracellular calcium concentration and induces apoptosis in pancreatic AR42J cells ; 4)pancreastatin inhibits secretagogues-induced rise in intracellular free calcium in single rat pancreatic islet cells ; 5)GLP-1 depolarizes rat pancreatic B-cells in a Na+dependent manner ; 6)bradykinin rises the intracellular calcium concentration of pancreatic acinar AR42J cells.