Studies on novel marine bioactive substances as pharmacological resources

我们分离和鉴定了几种海洋代谢物，并分析了它们的药理作用，以建立海洋新资源库。以下是我们的药理研究实例：1.贝毒素-2：贝毒素-2(Pectenooxin-2，PCTX-2)，它是从扇贝中分离出来的一种与腹泻性贝类中毒有关的聚醚大环内酯类毒素，非选择性地抑制血管平滑肌收缩。在A7r5细胞系中，FITC-Palloidine染色发现PCTX-2抑制了丝状肌动蛋白应激纤维的形成。PCTX-2可抑制肌动蛋白的聚合速度和程度。结论：1.透射电子显微镜观察显示，PCTX-2通过一层电子致密物质特异性损伤A7r5细胞中与根尖应力纤维相关的根尖质膜。瑞得他胺：研究了瑞得他胺的药理特性。瑞得他胺是一种新型海绵衍生的含有法尼基和生物碱的异戊二烯类化合物。ST-A(30-30μM)抑制CaM活性。而ST-C(30-300μM)和法尼醇(30-300μM)对酶活性影响不大。在大鼠主动脉平滑肌细胞系A7r5细胞中，这三种化合物在10μM时均显著抑制DVC。在贴片吸管中加入CaM可减弱ST-A对豚鼠回肠平滑肌细胞的抑制作用。这些结果表明，法尼醇和ST-C对VDC有直接抑制作用。相反，ST-A除了直接抑制VDC外，还通过CaM抑制VDC。

We have isolated and determined several marine metabolites, and analyzed their pharmacological actions to establish the library of novel marine resources. Following are the examples of our pharmacological studies;1. Pectenotoxin-2: Pectenotixin-2 (PCTX-2), which is one of polyether macrolide toxin isolated from scallops involved in diarrhetic shellfish poisoning, nonselectively inhibited vascular smooth muscle contractions. In A7r5 cell line, PCTX-2 suppressed filamentous actin stress fiber formation detected by FITC-phalloidine staining. PCTX-2 was found to inhibit the velocity and the degree of actin polymerization. Transmission electron microscopic observation disclosed that PCTX-2 specifically damaged apical plasma membranes associated with apical stress fibers via a mat of electron-dense materials in A7r5 cells.2. Stellettamides: Pharmacological feature of stellettamides, novel sponge derived isoprenoid derivatives containing farnesyl moiety and an alkaloid uni, was investigated. ST-A (30-30μM) inhibited CaM activity. In contrast, ST-C (30-300μM) and farnesol (30-300μM) had little effect on the activity. In the rat aortic smooth muscle cell lines, A7r5 cells, all three compounds significantly inhibited DVC at 10μM. Addition of CaM into the patch pipette reduced the inhibitory action by ST-A in guinea-pig ileal smooth muscle cells. These results indicated that farnesol and ST-C directly inhibits VDC. In contrast, ST-A inhibits VDC through CaM in addition to the direct inhibitory action.