Parks Lisa D, Zalups Rudolfs K, Barfuss Delon W
Biology Department, Georgia State University, Atlanta, Georgia.
Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.
J Am Soc Nephrol. 2000 Jun;11(6):1008-1015. doi: 10.1681/ASN.V1161008.
Lumen-to-bath and bath-to-lumen transport rates of glutathione (GSH) were measured in isolated perfused S(1), S(2), and S(3) segments of the rabbit proximal tubule. In lumen-to-bath experiments, the perfusion solution contained 4.6 microM (3)H-GSH with or without 1.0 mM acivicin. In all three segments perfused without acivicin, luminal disappearance rate (J(DL)) and bath appearance rate (J(AB)) of (3)H-GSH were 14.5 +/- 0.5 and 2.2 +/- 0.8 fmol/min per mm tubule length, respectively. With acivicin present, J(DL) and J(AB) were reduced to 1.3 +/- 0.4 and 0.5 +/- 0.3, respectively, with no differences among segments. Cellular concentrations of (3)H-GSH in S(1), S(2), and S(3) segments when acivicin was absent were 23.1 +/- 2.0, 31.7 +/- 11.4, and 143.5 +/- 17.9 microM, respectively. With acivicin in perfusate, cellular concentrations were reduced but there was no change in the heterogeneity profile. In bath-to-lumen transport experiments (S(2) segments only), the bathing solution contained 2.3 microM (3)H-GSH. (3)H-GSH appearance in the lumen (J(AL), fmol/min per mm) and cellular accumulation from the bath were studied with and without acivicin in the perfusate. J(AL) values were 3.0 +/- 0.2 and 0.2 +/- 0.03 while cellular concentrations were 9.5 +/- 1.0 and 6.1 +/- 0.5 microM, respectively. It is concluded that: (1) GSH is primarily removed from the luminal fluid after degradation to glycine, cysteine, and glutamate, which are absorbed; (2) GSH can be absorbed intact at the luminal membrane; (3) the S(3) segment has the greatest GSH cellular concentration because its basolateral membrane has less capacity for cell-to-bath transport of GSH; and (4) GSH can be secreted intact from the peritubular compartment into the tubular lumen.
在兔近端小管分离的灌注S(1)、S(2)和S(3)节段中测量了谷胱甘肽（GSH）的管腔到浴和浴到管腔的转运速率。在管腔到浴的实验中，灌注液含有4.6 microM （3）H-GSH，有或没有1.0 mM阿西维辛。在所有三个未用阿西维辛灌注的节段中，（3）H-GSH的管腔消失率（J(DL)）和浴出现率（J(AB)）分别为每毫米小管长度14.5±0.5和2.2±0.8 fmol/分钟。存在阿西维辛时，J(DL)和J(AB)分别降至1.3±0.4和0.5±0.3，各节段之间无差异。不存在阿西维辛时，S(1)、S(2)和S(3)节段中（3）H-GSH的细胞浓度分别为23.1±2.0、31.7±11.4和143.5±17.9 microM。灌注液中存在阿西维辛时，细胞浓度降低，但异质性分布没有变化。在浴到管腔的转运实验中（仅S(2)节段），浴液含有2.3 microM （3）H-GSH。研究了灌注液中有或没有阿西维辛时（3）H-GSH在管腔中的出现（J(AL)，每毫米fmol/分钟）和从浴中细胞积累的情况。J(AL)值分别为3.0±0.2和0.2±0.03，而细胞浓度分别为9.5±1.0和6.1±0.5 microM。得出以下结论：（1）GSH主要在降解为甘氨酸、半胱氨酸和谷氨酸后从管腔液中去除，这些物质被吸收；（2）GSH可以在管腔膜完整吸收；（3）S(3)节段的GSH细胞浓度最高，因为其基底外侧膜对GSH的细胞到浴转运能力较低；（4）GSH可以从肾小管周围隔室完整分泌到肾小管腔中。
