Luminal transport step of para-aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo
Luminal transport step of para-aminohippurate (PAH): transport from PAH-loaded proximal tubular cells into the tubular lumen of the rat kidney in vivo
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对氨基马尿酸 (PAH) 的管腔转运步骤：从负载 PAH 的近端肾小管细胞转运至体内大鼠肾的肾小管腔
DOI：
10.1007/s004240050339
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
G. Rumrich
中科院分区：
文献类型：
--
作者：
K. Ullrich;G. Rumrich
用含[~H]-对氨基马尿酸([~H]-PAH)的林格液微灌流近端肾小管上皮细胞10个S的近端肾小管上皮细胞( 近端肾小管)。在此之后，立即通过在接触1-10 S时间后再次吸入液体来测量从细胞流入到注入充满油的管腔的平衡溶液的柱中的多环芳烃。在接触时间为2 S的时间内，管腔内多环芳烃浓度几乎呈线性上升，在2 S后达到1.6，在5 S后达到3.2，不同动作对近端肾小管上皮细胞去极化的2 S多环芳烃浓度比没有影响。2-S多环芳烃浓度比不受灌流液pH值的影响，也不受灌流液中氯离子浓度从0到134 mmo1/L的影响，也不受灌流液中含有5 mmo1/L尿酸盐和25 mmo1/L乳酸的影响。灌流液中加入25或50 mmol/S HCO3-(-50%)时，2-L多环芳烃的浓度比下降，即反式抑制作用。5 mmol/L的取代苯甲酸酯：2-羟基苯甲酸酯(-58%)、2-甲氧基苯甲酸酯(-46%)、2-羟基苯甲酸乙酰酯(-36%)、2-羟基-3，5-二硝基苯甲酸酯(-48%)、3，5-二氯苯甲酸酯(-49%)和2，3，5-三氯苯甲酸酯(-45%)也有反式抑制作用。对苯甲酸酯、3-羟基苯甲酸酯、2-氯苯甲酸酯、2-硝基苯甲酸酯、2，5-二硝基苯甲酸酯、3-氨基甲酰苯甲酸酯和4-氨基甲酰苯甲酸酯无影响。然而，后两个具有两个额外侧基的类似物，如速尿和哌拉尼德，或疏水部分，如丙磺舒，是抑制作用的(分别为-62，-41和-49%)。苯氧基乙酸酯没有作用；然而，如果它另外含有三个氯基，如2，4，5-三氯苯氧基乙酸酯(-71%)或疏水氨基甲酰侧基，如山梨酸(salyrgan，-75%)，则它可抑制。苯磺酸反式抑制(-33%)，酚红(-39%)和磺基荧光素(-55%)也是如此。然而，相应的羧基化合物没有反式抑制作用(酚酞)或较弱(荧光素，-42%)。尿酸(-53%)、替尼酸(-55%)、吲哚醌(-72%)和苯溴马龙(-42%)的反式抑制作用可归因于苯环上的两个氯或溴侧基。其他反式抑制尿酸的物质有吲哚美辛(-42%)、磺胺吡喃酮(-38%)、氯沙坦(-80%)及其代谢物EXP 3174(-55%)和AA 193(-65%)。这些有机酸的pKa值在2.8~4.9之间，具有氯基和亚硫基，以及杂环5环和疏水环或链区。5 mmoL/L PAH、2-氧代戊二酸、DIDS、cGMP、前列腺素E_2、皮质醇、苄基米洛利、吡嗪酸和25 mmoL/L乳酸盐对上述指标无明显影响。我们的数据表明，在原位，多环芳烃的分泌腔转运是以一种非流变性的方式进行的，通过阴离子交换。观察到的PAH分泌的反式抑制似乎与对腔PAH转运体的亲和力以及对尿尿酸物质的尿尿酸效力有关。
Abstract Proximal tubular cells were loaded for 10 s with [3H]para-aminohippurate ([3H]PAH) by microperfusing the peritubular capillaries with Ringer solution containing 0.05 mmol/l PAH. Immediately thereafter [3H]PAH influx from cells into a column of equilibrium solution injected into the oil-filled tubular lumen was measured by re-aspirating the fluid after 1–10 s of contact time. The rise of luminal PAH concentration within 2 s of contact time was almost linear, reaching a luminal / capillary concentation ratio of 1.6 after 2 s and of 3.2 after 5 s. The 2-s PAH concentration ratio was not changed when different manoeuvres were applied to depolarize proximal tubular cells. Also, the 2-s PAH concentration ratio was not influenced by varying the luminal pH from 6.0 to 8.0 or the luminal Cl–concentration from zero to 134 mmol/l or when either 5 mmol/l urate or 25 mmol/l lactate was in the luminal perfusate. A decrease in the 2-s PAH concentration ratio, i.e. trans-inhibition, was observed when 25 or 50 mmol/l HCO3–(–50%) was in the luminal perfusate. Trans-inhibition was also seen with 5 mmol/l of the following substituted benzoates: 2-hydroxy-benzoate (–58%), 2-methoxy-benzoate (–46%), 2-hydroxy-benzoate-acetyl ester (–36%), 2-hydroxy-3,5-dinitro-benzoate (–48%), 3,5-dichloro-benzoate (–49%), and 2,3,5-trichloro-benzoate (–45%). No effect was seen with benzoate, 3-hydroxy-benzoate, 2-chloro-benzoate, 2-nitro-benzoate, 2,5-dinitro-benzoate, 3-sulfamoyl-benzoate and 4-sulfamoyl-benzoate. However, analogues of the latter two compounds possessing two additional side groups, such as furosemide and piretanide, or a hydrophobic moiety, such as probenecid, were inhibitory (by –62, –41 and –49% respectively). Phenoxyacetate had no effect; however, it inhibited if in addition it had three chloro groups, as in 2,4,5-trichlorophenoxyacetate (–71%) or a hydrophobic carbamoyl side group, as in mersalylic acid (salyrgan, –75%). Benzene-sulfonate trans-inhibited (–33%), as did phenolsulfonphthalein (phenol red, –39%) and sulfofluorescein (–55%). However, the trans-inhibitory effect of the corresponding carboxy-compounds was absent (phenolphthalein) or weaker (fluorescein, –42%). The trans-inhibitory effect of the uricosurics ethacrynic acid (–53%), tienilic acid (–55%) indacrinone (–72%) and benzbromarone (–42%) could be attributed to two chloro or bromo side groups on the benzene ring. Other trans-inhibiting uricosuric substances were indomethacin (–42%), sulfinpyrazone (–38%), losartan (–80%) its metabolite EXP 3174 (–55%), and AA 193 (–65%). These organic acids, with pKa values between 2.8 and 4.9, possess chloro and sulfin groups, as well as heterocyclic 5-ring and hydrophobic ring or chain areas. No significant effect was seen with 5 mmol/l PAH, 2-oxo-glutarate, DIDS, cGMP, prostaglandin E2, cortisol, benzylamiloride, pyrazinoic acid and 25 mmol/l lactate. Our data indicate that in situ the secretory luminal PAH transport proceeds in a non-rheogenic fashion, per exclusionem by anion exchange. The observed trans-inhibition of PAH secretion seems to correlate with the affinity for the luminal PAH transporter and, for uricosuric substances, with their uricosuric potency.
狗肾微绒毛膜囊泡中通过阴离子交换的尿酸盐转运。
DOI：
10.1152/ajprenal.1983.244.1.f56
发表时间：
1983
期刊：
The American journal of physiology
影响因子：
--
作者：
Kahn,AM;Aronson,PS
通讯作者：
Aronson,PS
抑制剂对兔肾刷状缘膜囊泡阴离子交换剂的影响。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
McConnell,KR;Aronson,PS
通讯作者：
Aronson,PS
用秋水仙碱的光活性类似物对多药耐药细胞中的 P-糖蛋白进行光亲和标记。
DOI：
10.1016/0006-291x(89)90830-9
发表时间：
1989
影响因子：
3.1
作者：
Safa,AR;Mehta,ND;Agresti,M
通讯作者：
Agresti,M