Ito S, Koren G, Harper P A, Silverman M
Department of Paediatrics and Pharmacology, Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Can J Physiol Pharmacol. 1993 Jan;71(1):40-7. doi: 10.1139/y93-006.
Digoxin secretory transport across renal tubular cell monolayers (LLC-PK1) grown on permeable filters was characterized. Metabolic inhibitors reduced total and specific basolateral to apical (B-A) flux of digoxin and conversely increased the apical to basolateral (A-B) flux. The specific transport of digoxin from the basolateral to the apical compartment was saturable, with a maximum velocity of transport of 184.5 +/- 38.0 pmol.cm-2.h-1 and a Michaelis-Menten constant (Km) of 14.1 +/- 1.6 microM. In addition, B-A flux of digoxin resulted in accumulation of digoxin in the apical compartment against the concentration gradient. P-Glycoprotein inhibitors such as quinidine, verapamil, vincristine, and cyclosporine increased the net A-B flux and inhibited the total B-A flux without affecting the nonspecific flux significantly. Tetraethylammonium, a prototype substrate for an organic cation transport system, had no such effect. Our results suggest that digoxin undergoes transepithelial secretion by an energy-dependent, carrier-mediated process in renal tubules, a process that seems to be distinct from the tetraethylammonium transport system.
对生长在可渗透滤膜上的肾小管细胞单层（LLC-PK1）中地高辛的分泌转运进行了表征。代谢抑制剂降低了地高辛从基底外侧到顶端（B-A）的总通量和特异性通量，反之增加了从顶端到基底外侧（A-B）的通量。地高辛从基底外侧到顶端隔室的特异性转运是可饱和的，最大转运速度为184.5±38.0 pmol·cm⁻²·h⁻¹，米氏常数（Km）为14.1±1.6 μM。此外，地高辛的B-A通量导致地高辛在顶端隔室中逆浓度梯度积累。奎尼丁、维拉帕米、长春新碱和环孢素等P-糖蛋白抑制剂增加了净A-B通量并抑制了总B-A通量，而对非特异性通量没有显著影响。有机阳离子转运系统的原型底物四乙铵没有这种作用。我们的结果表明，地高辛在肾小管中通过能量依赖的、载体介导的过程进行跨上皮分泌，这一过程似乎与四乙铵转运系统不同。
