Okudaira N, Sawada Y, Sugiyama Y, Iga T, Hanano M
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biochim Biophys Acta. 1989 May 19;981(1):1-7. doi: 10.1016/0005-2736(89)90074-6.
The effect of procainamide on renal tubular transport of cimetidine was studied in isolated perfused rat kidney based on the multiple indicator dilution (MID) technique. T-1824-labeled albumin (a vascular reference), [14C]creatine (an extracellular reference), and [3H]cimetidine were rapidly injected into the renal artery of isolated perfused rat kidney in the presence or absence of procainamide (100 microM) in the perfusate, and normalized outflow-time patterns were secured from rapidly sampled renal perfusate. A distributed two-compartmental model was fitted to the dilution data by non-linear least-squares regression, and the influx, efflux and sequestration rate constants were estimated. Net transport and influx processes of cimetidine were competitively inhibited by procainamide (PA), while the efflux and sequestration processes were increased. The increase in the values of the efflux and sequestration rate constants by addition of procainamide may be explained by the increase in the tissue binding of cimetidine. However, these three processes were not significantly affected by p-aminohippurate (PAH). These results suggest that both cimetidine and procainamide are secreted into the lumen by an organic base transport mechanism in the perfused kidney, in which the spatial organization and cell polarity of the kidney are maintained.
基于多指示剂稀释（MID）技术，在离体灌注大鼠肾脏中研究了普鲁卡因胺对西咪替丁肾小管转运的影响。在灌注液中存在或不存在普鲁卡因胺（100微摩尔）的情况下，将T-1824标记的白蛋白（一种血管标志物）、[14C]肌酸（一种细胞外标志物）和[3H]西咪替丁快速注入离体灌注大鼠肾脏的肾动脉，并从快速采集的肾灌注液中获得标准化的流出时间模式。通过非线性最小二乘回归将一个分布式双室模型拟合到稀释数据中，并估计流入、流出和隔离速率常数。西咪替丁的净转运和流入过程受到普鲁卡因胺（PA）的竞争性抑制，而流出和隔离过程则增加。添加普鲁卡因胺后流出和隔离速率常数的值增加可能是由于西咪替丁组织结合增加所致。然而，这三个过程不受对氨基马尿酸（PAH）的显著影响。这些结果表明，在灌注肾脏中，西咪替丁和普鲁卡因胺均通过有机碱转运机制分泌到管腔中，其中肾脏的空间组织和细胞极性得以维持。
