Cimetidine transport in isolated luminal membrane vesicles from rabbit kidney.
Cimetidine transport in isolated luminal membrane vesicles from rabbit kidney.
复制标题
西咪替丁在兔肾分离的管腔膜囊泡中的转运。
DOI：
10.1152/ajprenal.1987.253.1.f141
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Giacomini,KM
中科院分区：
文献类型：
--
作者：
Gisclon,L;Wong,FM;Giacomini,KM
进行实验研究组胺 H2 受体拮抗剂西咪替丁在兔肾皮质制备的管腔膜囊泡中的转运。随着时间的推移，西咪替丁在囊泡中积累。西咪替丁的摄取对囊泡大小的变化敏感，表明该化合物被转运到具有渗透反应性的囊泡内空间。其吸收率可以用饱和过程和非饱和过程来描述。 Km 为 4.6 +/- 4.0 microM，Vmax 为 6.8 +/- 2.3 pmol X s-1 X mg Protein-1（平均值 +/- SD，n = 4）。 N1-甲基烟酰胺（NMN）、西咪替丁、西咪替丁亚砜和雷尼替丁抑制西咪替丁的摄取。在预载有较高浓度的未标记西咪替丁(2.4 X 10(-4) M)的囊泡中，在存在向外定向质子梯度的情况下，西咪替丁的摄取增强。向外的质子梯度将西咪替丁的摄取增强至超过其平衡积累的值。以这种方式刺激的摄取可以被阳离子、NMN、碱、雷尼替丁和西咪替丁亚砜抑制，有趣的是，还可以被阴离子、丙磺舒抑制。丙磺舒的作用似乎并不是由于对膜结合、膜电位或囊泡大小的非特异性影响。这些数据与在分离的灌注近端小管中获得的数据一致，证明丙磺舒抑制西咪替丁转运。本研究的数据表明，丙磺舒对西咪替丁转运的影响特别涉及管腔膜中的转运蛋白。
Experiments were conducted to study the transport of the histamine H2-receptor antagonist, cimetidine, in luminal membrane vesicles prepared from rabbit renal cortex. Cimetidine accumulated in the vesicles with time. Cimetidine uptake was sensitive to changes in vesicle size, suggesting that the compound is transported into an osmotically reactive intravesicular space. Its rate of uptake could be described by both a saturable and a nonsaturable process. The Km was 4.6 +/- 4.0 microM and the Vmax was 6.8 +/- 2.3 pmol X s-1 X mg protein-1 (mean +/- SD, n = 4). N1-methylnicotinamide (NMN), cimetidine, cimetidine sulfoxide, and ranitidine inhibited the uptake of cimetidine. Cimetidine uptake in the presence of an outwardly directed proton gradient was enhanced in vesicles preloaded with a higher concentration of unlabeled cimetidine (2.4 X 10(-4) M). An outwardly directed proton gradient enhanced the uptake of cimetidine to values exceeding its equilibrium accumulation. Uptake stimulated in this way could be inhibited by the cation, NMN, the bases, ranitidine, and cimetidine sulfoxide, and interestingly, by the anion, probenecid. The effect of probenecid did not appear to be due to nonspecific effects on membrane binding, membrane potential, or vesicle size. These data are consistent with data obtained in isolated perfused proximal tubules, demonstrating that probenecid inhibits cimetidine transport. The data in this study suggest that the effect of probenecid on cimetidine transport specifically involves the transporter in the luminal membrane.