Harder A, Goossens J, Andrews P
Bayer AG, Institut für Parasitologie, Bayerwerk, F.R.G.
Mol Biochem Parasitol. 1988 May;29(1):55-9. doi: 10.1016/0166-6851(88)90119-3.
Praziquantel induces a bilayer to isotropic transition in the absence of Ca2+ in a mixed phospholipid membrane consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS) at a molar ratio of 2:1 at 25 degrees C or 35 degrees C, irrespective of the lipid/drug molar ratio (10:1; 2:1). Addition of Ca2+ at different PS/Ca2+ molar ratios (4:1, 2:1 or 1:1) leads to a transition to a hexagonal (HII) state. With a phospholipid membrane of different composition (PE/PS molar ratio 4:1) praziquantel exerts quite different effects in the presence of Ca2+ (PS/Ca2+ molar ratio 1:1). An isotropic-signal appears together with a bilayer one at 25 degrees C, while a HII-signal can be detected at 35 degrees C. Thus, two separate phases coexist at this PE/PS molar ratio, while at a PE/PS molar ratio of 2:1, praziquantel and Ca2+ induce only a HII-signal. The results with these model membranes show that praziquantel and Ca2+ exert drastic influences on bilayer-isotropic-hexagonal transitions. The possibility that this drug might act in the schistosomal tegumental membranes in the same way is discussed.
在25℃或35℃下，吡喹酮在由摩尔比为2:1的磷脂酰乙醇胺（PE）和磷脂酰丝氨酸（PS）组成的混合磷脂膜中，在不存在Ca2+的情况下诱导双层向各向同性转变，与脂质/药物摩尔比（10:1；2:1）无关。以不同的PS/Ca2+摩尔比（4:1、2:1或1:1）添加Ca2+会导致向六方（HII）态转变。对于不同组成的磷脂膜（PE/PS摩尔比为4:1），吡喹酮在存在Ca2+（PS/Ca2+摩尔比为1:1）时会产生截然不同的影响。在25℃时，各向同性信号与双层信号同时出现，而在35℃时可检测到HII信号。因此，在这个PE/PS摩尔比下两个不同的相共存，而在PE/PS摩尔比为2:1时，吡喹酮和Ca2+仅诱导出HII信号。这些模型膜的结果表明，吡喹酮和Ca2+对双层-各向同性-六方转变有显著影响。文中讨论了这种药物可能以同样方式作用于血吸虫体被膜的可能性。
