Hugonin Loïc, Vukojević Vladana, Bakalkin Georgy, Gräslund Astrid
Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, S-10691 Stockholm, Sweden.
Biochim Biophys Acta. 2008 May;1778(5):1267-73. doi: 10.1016/j.bbamem.2008.02.003. Epub 2008 Feb 21.
Dynorphins, endogeneous opioid peptides, function as ligands to the opioid kappa receptors but also induce non-opioid excitotoxic effects. Dynorphin A can increase the intra-neuronal calcium concentration through a non-opioid and non-NMDA mechanism. In this investigation, we show that big dynorphin, dynorphin A and to some extent dynorphin A (1-13), but not dynorphin B, allow calcium to enter into large unilamellar phospholipid vesicles with partly negative headgroups. The effects parallel the previously studied potency of dynorphins to translocate through biological membranes and to cause calcein leakage from large unilamellar phospholipid vesicles. There is no calcium ion influx into vesicles with zwitterionic headgroups. We have also investigated if the dynorphins can translocate through the vesicle membranes and estimated the relative strength of interaction of the peptides with the vesicles by fluorescence resonance energy transfer. The results show that dynorphins do not translocate in this membrane model system. There is a strong electrostatic contribution to the interaction of the peptides with the membrane model system.
强啡肽作为内源性阿片肽，不仅可作为阿片κ受体的配体，还能诱导非阿片类兴奋毒性作用。强啡肽A可通过非阿片类且非N-甲基-D-天冬氨酸（NMDA）的机制增加神经元内的钙浓度。在本研究中，我们发现大分子强啡肽、强啡肽A以及在一定程度上强啡肽A（1-13），而非强啡肽B，能使钙进入部分头部基团带负电的大单层磷脂囊泡。这些作用与先前研究的强啡肽穿过生物膜以及导致钙黄绿素从大单层磷脂囊泡泄漏的效力平行。对于头部基团为两性离子的囊泡，没有钙离子流入。我们还研究了强啡肽是否能穿过囊泡膜，并通过荧光共振能量转移估计了肽与囊泡相互作用的相对强度。结果表明，在这个膜模型系统中强啡肽不会发生转运。肽与膜模型系统的相互作用存在很强的静电作用。
