Adsorption of aminopyridines to phosphatidylserine membranes.
Adsorption of aminopyridines to phosphatidylserine membranes.
复制标题
氨基吡啶对磷脂酰丝氨酸膜的吸附。
DOI：
10.1016/0005-2736(90)90162-h
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Bennett,MJ
中科院分区：
文献类型：
--
作者：
Smejtek,P;Riker,WK;Wright,C;Bennett,MJ
氨基吡啶类化合物属于在低钙浓度下促进突触传递的化合物，这种作用与阻断 K+ 通道、增强钙进入突触前末梢以及更多地释放递质有关。我们测量了在氨基吡啶和一些相关化合物存在下磷脂酰丝氨酸囊泡的 zeta 电位，以便将氨基吡啶的缔合强度与其生物有效性联系起来。根据 Langmuir-Stern-Grahame 吸附模型分析了 Zeta 电位对氨基吡啶浓度的依赖性。研究中获得的关联常数（以M−1为单位）的排序如下：3,4-二氨基吡啶（6.5）、4,5-二氨基吡啶（3.8）、4-氨基吡啶（2.6）、3-氨基吡啶（1.8）、2-氨基吡啶（1.6）、4-二甲基氨基吡啶（0.5）、4-氨基吡啶甲硫氨酸 (0.2)，以及作为对照的钙 (12.1)。将缔合常数与已发表的 CNDO/2 方法获得的电势图结果进行比较表明，与磷脂酰丝氨酸膜的结合随着质子化氨基吡啶环上过量电荷的密度而增加。我们发现氨基吡啶阻断K+通道、释放递质以及突触传递的钙浓度依赖性变化的效力顺序与与磷脂酰丝氨酸膜的关联常数的顺序大致相同。假设突触前末端的氨基吡啶结合域具有与磷脂酰丝氨酸膜相似的吸附特性，我们估计该域与外部溶液之间的电势差在—300和—340 mV之间。
Aminopyridines belong to the class of compounds which facilitate synaptic transmission at low calcium concentration, an effect associated with the block of K+channels, enhanced entry of calcium into presynaptic terminals and greater release of transmitter. We have measured the zeta-potential of phosphatidylserine vesicles in the presence of aminopyridines and some related compounds in order to relate the strength of association of the aminopyridines with their biological effectiveness. The dependence of zeta-potential on the concentration of aminopyridines was analyzed in terms of the Langmuir-Stern-Grahame adsorption model. The rank order of the association constants (in M−1) obtained in the study was as follows: 3,4-diaminopyridine (6.5), 4,5-diaminopyrimidine (3.8), 4-aminopyridine (2.6), 3-aminopyridine (1.8), 2-aminopyridine (1.6), 4-dimethylaminopyridine (0.5), 4-aminopyridine methiodide (0.2), and, as control, calcium (12.1). The comparison of association constants with published results of the electric potential maps obtained by the CNDO / 2 method suggests that binding to phosphatidylserine membrane increases with the density of excess charge on the protonated aminopyridine ring. We find that the sequence of potencies of aminopyridines in blocking K+channels, in releasing transmitter, and in the shifts of calcium concentration dependence of synaptic transmission are about the same as the sequence of association constants with the phosphatidylserine membrane. Assuming that the binding domain for aminopyridines in the presynaptic terminal has similar adsorption properties as the phosphatidylserine membrane, we estimate the electric potential difference between the domain and the external solution to be between —300 and —340 mV.