Clinical Chemistry of Newly-found Esterase for Endogenous Digitalis-like Factor

内源性洋地黄样因子(EDLF)是水盐代谢的重要调节因子。最近的研究表明，内源性洋地黄样因子是由洋地黄内酯和蟾酥内酯组成的。近年来，我们发现中华钳蝎毒素(MBT)是EDLF的新成员。该化合物的结构经串联液相色谱-质谱联用信号和核磁共振分析确证。有趣的是，这种化合物由强心类固醇和氨基酸组成，阿根廷。并搜索了该侧链的酯酶。这种与组织激肽释放酶类似的酯酶与胆固醇酯酶等其他酯酶的反应相对较慢，其生理意义尚不明确。但我们利用SHR大鼠发现肾素-血管紧张素系统(RAS)和MBT在高血压中的作用。血管紧张素受体阻滞剂替米沙坦组血浆MBT水平低于对照组。2周和4周后尿MBT排泄量增加，但ARB修饰后的MBT排泄量没有增加，血压也没有升高。这些结果提示，MBT参与了RAS的SHR的调控机制。该分析系统也应用于临床毒理学领域。

Endogenous digitalis-like factor (EDLF) act as important modulator for water and salt metabolism. From recent studies endogenous digitalis-like factor is consisted of cardenolides and bufadienolides. Recently we found marinobufotoxin (MBT) as the new member of EDLF. The structure of this compound was confirmed by tandem mass spectrometric signals of liquid chromatography-mass spectrometry and nuclear magnetic resonance (NMR) analysis. Interestingly this compound consists of cardiotonic steroid with C6-chain and amino acids, argentine. And the esterase for this side chain was searched. The reaction of this esterase mimicked by the tissue kallikrein and other esterases such as cholesterol esterase were relatively slow and the physiological meanings are still ambiguous. But we found the contribution of rennin-angiotensin system (RAS) and MBT on hypertension with use of SHR rats. In the angiotensin-receptor blocker (ARB), telmisartan group, the plasma level of MBT was lower than that in the control group. The urine MBT excretion increase after 2 and 4 weeks but the MBT excretion modified by the ARB did not increase and the blood pressure did not increase. These results suggested that MBT contributed the control mechanism in SHR with RAS. And this analytic system was also applied to clinical toxicology area.