Transport of cimetidine by the rat choroid plexus in vitro.
Transport of cimetidine by the rat choroid plexus in vitro.
复制标题
大鼠脉络丛体外转运西咪替丁。
DOI：
10.1007/978-88-470-2103-7_27
复制
发表时间：
1986
期刊：
影响因子：
--
通讯作者：
M. Hanano
中科院分区：
文献类型：
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作者：
H. Suzuki;Y. Sawada;Y. Sugiyama;T. Iga;M. Hanano
为了表征西咪替丁（一种有机阳离子）在血-脑脊液屏障中的转运系统，研究了西咪替丁在离体大鼠脉络丛中的蓄积。西咪替丁的蓄积是通过一个饱和过程（Km = 53 μ M，Vmax = 12 nmol/ml/min）逆浓度梯度进行的，该过程可被巯基试剂（对羟基汞苯甲酸盐）、代谢抑制剂（KCN和2，4-二硝基苯酚）和低温（Q10 = 4.5）抑制，但不需要向内的Na+梯度。有机阳离子，如1 N-甲基烟酰胺，四乙铵，胆碱，组胺和肌酐不影响西咪替丁的积累在1 mM的浓度。西咪替丁不影响四乙铵的积累。更多的亲脂性阳离子，如奎尼丁和奎宁不仅抑制西咪替丁的积累，但也是一种有机阴离子，苄青霉素，虽然抑制机制尚不清楚。1毫摩尔的有机阴离子，如5-羟基吲哚乙酸，对氨基马尿酸，高香草酸，水杨酸和青霉素，抑制西咪替丁的积累。此外，有机阴离子（青霉素和水杨酸）的积累表现出饱和性，并被西咪替丁抑制。西咪替丁和有机阴离子表现出相互抑制作用。寡肽也抑制西咪替丁的积累。这些结果表明，西咪替丁在脉络丛中的转运是通过载体介导的主动转运过程，而不需要向内的Na+梯度。这种转运被几种具有不同性质的化合物抑制，如寡肽、亲脂性阳离子和有机阴离子，尽管抑制机制尚不清楚。
To characterize the transport system of cimetidine, an organic cation, in the blood-cerebrospinal fluid barrier, the accumulation of cimetidine by the isolated rat choroid plexus was examined. Accumulation of cimetidine was against a concentration gradient via a saturable process (Km = 53 microM, Vmax = 12 nmol/ml/min) that was inhibited by sulfhydryl reagents (p-hydroxymercuribenzoate), metabolic inhibitors (KCN and 2,4-dinitrophenol) and hypothermia (Q10 = 4.5), but did not require inward Na+ gradient. Organic cations such as 1N-methylnicotinamide, tetraethylammonium, choline, histamine and creatinine did not affect the accumulation of cimetidine at the concentration of 1 mM. Cimetidine did not affect the accumulation of tetraethylammonium. More lipophilic cations such as quinidine and quinine inhibited not only the accumulation of cimetidine but also that of an organic anion, benzylpenicillin, although the inhibitory mechanisms are not known. One millimolar of organic anions, such as 5-hydroxyindoleacetic acid, p-aminohippuric acid, homovanillic acid, salicylic acid and benzylpenicillin, inhibited the accumulation of cimetidine. Furthermore, the accumulation of organic anions (benzylpenicillin and salicylic acid) showed saturability and was inhibited by cimetidine. Cimetidine and the organic anions thus showed a mutual inhibition. Oligopeptides also inhibited the accumulation of cimetidine. These findings suggested that cimetidine transport in the choroid plexus is via carrier-mediated active transport process, but does not require inward Na+ gradient. This transport is inhibited by several compounds with different properties like oligopeptides, lipophilic cations and organic anions, although the inhibitory mechanism is not known.