中文摘要：

利用海藻来源的黄曲霉中提取到的次级代谢产物筛选GPR41的激动剂，发现环二肽类化合物环（L-脯-L-苯丙）二肽（17号）可在多种（G41-CHO，G12-CHO，Mock—CHO，SH—sy5Y和HEK293）细胞中引起细胞内cAMP水平升高．实验结果表明，17号化合物引起cAMP升高不依赖于GPCR的激活，且腺苷酸环化酶激活剂forskolin与17号化合物共处理组比fsk单独处理组cAMP进一步增加．实验结果提示，17号化合物可能是通过抑制cAMP水解，从而引起cAMP水平的持续升高．17号化合物与已知的PDE抑制剂具有相似的结构特征，可能是潜在的磷酸二酯酶抑制剂．这是首次发现环（L-脯-L-苯丙）二肽具有在多种细胞内提高cAMP浓度的作用．

英文摘要：

A stable GPR41 receptor cell line was used to screen candidate agonist from the sec- ondary metabolites extracted from gulf seaweed aflatoxin c-f-3 in Putian Fujian. The cAMP results have shown that the No. 17 compound Cyclo （L-Pro-L-Phe）, belonging to cyclic dipeptide, is able to increase intracellular cAMP in a variety of cells （including G41-CHO, G12-CHO, Mock-CHO, SH-sySy and HEK293）. We have demonstrated that No. 17 compound induced cAMP increase in a GPCR-independent manner. Co-adminstration of adenylate cyclase activating agent forskolin and No. 17 compound can lead to a further increase in cAMP level compared with those treated with forskolin alone. These results have suggested that No. 17 compound may in duce a sustained elevation of cAMP levels by inhibiting cAMP hydrolysis. Since No. 17 compound shared similar chemical structures with some known PDE inhibitors, which may be a potential of phosphodiesterase inhibitors. This is the first report that Cyclo（L-Pro-L-Phe） could regulate cAMP formation in a variety of cells （G41-CHO, G12-CHO, Mock-CHO, SH-syfy and HEK293）.