Inui K, Terada T, Masuda S, Saito H
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Nephrol Dial Transplant. 2000;15 Suppl 6:11-3. doi: 10.1093/ndt/15.suppl_6.11.
The H+/peptide co-transporters PEPT1 and PEPT2 mediate the cellular uptake of small peptides and peptide-like drugs from the glomerular filtrates. In the present study, we investigated the physiological and pharmacological implications of both transporters. (i) Comparison of the substrate affinity of PEPT1 and PEPT2 indicated that PEPT2 had higher affinity than PEPT1 for most substrates. (ii) The transport characteristics of beta-lactam antibiotics in the renal brush border membrane vesicles were well correlated with those in a PEPT2-expressing transfectant. These results suggested that PEPT2 predominantly contributed to reabsorption of beta-lactam antibiotics in the kidney at therapeutic concentrations. (iii) In rats with chronic renal failure, glycylsarcosine (Gly-Sar) uptake by the renal brush border membranes vesicles was maintained, whereas Na+-dependent glucose uptake was markedly reduced. It is therefore speculated that the function of peptide transporters is tolerant to chronic renal failure.
氢离子/肽共转运体PEPT1和PEPT2介导肾小球滤液中小肽和类肽药物的细胞摄取。在本研究中，我们调查了这两种转运体的生理和药理学意义。（i）PEPT1和PEPT2底物亲和力的比较表明，对于大多数底物，PEPT2比PEPT1具有更高的亲和力。（ii）β-内酰胺类抗生素在肾刷状缘膜囊泡中的转运特性与在表达PEPT2的转染子中的转运特性高度相关。这些结果表明，在治疗浓度下，PEPT2主要促进肾脏中β-内酰胺类抗生素的重吸收。（iii）在慢性肾衰竭大鼠中，肾刷状缘膜囊泡对甘氨酰肌氨酸（Gly-Sar）的摄取得以维持，而钠依赖性葡萄糖摄取则显著减少。因此推测，肽转运体的功能对慢性肾衰竭具有耐受性。
