Dawson M A, Renfro J L
Marine/Freshwater Biomedical Sciences Center, University of Connecticut, Storrs.
J Pharmacol Exp Ther. 1993 Aug;266(2):673-7.
We assessed the interaction of several pesticides with renal organic anion transport based on inhibition of the active transepithelial transport of p-aminohippuric acid ([3H]PAH) by primary cultures of winter flounder proximal tubules. Four structurally similar chlorophenoxy acid herbicides were tested. 2-Methyl-4-chlorophenoxyacetic acid at 0.1 mM had no effect on PAH transport. 2-(2,4-Dichlorophenoxy)propionic acid, 2-(2-methyl,4-chlorophenoxy)propionic acid and 2,4-dichlorophenoxyacetic acid inhibited PAH secretion with IC50 values (median inhibitory concentrations) of 0.09, 0.2 and 0.2 mM, respectively. At 2-(2-methyl,4-chlorophenoxy)propionic acid concentrations of 10(-7) to 10(-6) M, PAH secretion was stimulated to 132 and 139% of controls, respectively, at 2 hr. 2,2-bis-p-Chlorophenylacetic acid was tested at concentrations of 10(-7) to 10(-3) M and inhibited with an IC50 of 0.02 mM. At 10(-7) M 2,2-bis-p-chlorophenylacetic acid, a delayed increase was again seen in which PAH secretion increased to 154% of control at 2 hr. The anticholinesterase insecticide phosphothioic acid O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl ester), its more active metabolite O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphate and its dimethyl analog, phosphothioic acid O,O-dimethyl-O-(3,5,6-trichloro-2-pyridinyl ester) were tested at 0.1 mM. Phosphothioic acid O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl ester) increased PAH secretion significantly to 115% of control whereas the O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphate inhibited by 28%.(ABSTRACT TRUNCATED AT 250 WORDS)
我们基于冬季比目鱼近端小管原代培养物对对氨基马尿酸（[3H]PAH）主动跨上皮转运的抑制作用，评估了几种农药与肾脏有机阴离子转运的相互作用。测试了四种结构相似的氯苯氧基酸除草剂。0.1 mM的2-甲基-4-氯苯氧基乙酸对PAH转运无影响。2-(2,4-二氯苯氧基)丙酸、2-(2-甲基,4-氯苯氧基)丙酸和2,4-二氯苯氧基乙酸抑制PAH分泌，其IC50值（半数抑制浓度）分别为0.09、0.2和0.2 mM。在2-(2-甲基,4-氯苯氧基)丙酸浓度为10(-7)至10(-6) M时，2小时后PAH分泌分别被刺激至对照的132%和139%。测试了2,2-双对氯苯乙酸在10(-7)至10(-3) M浓度下的情况，其IC50为0.02 mM。在10(-7) M的2,2-双对氯苯乙酸作用下，再次观察到延迟增加，2小时时PAH分泌增加至对照的154%。抗胆碱酯酶杀虫剂硫代磷酸O,O-二乙基-O-(3,5,6-三氯-2-吡啶基酯)、其活性更高的代谢产物O,O-二乙基-O-(3,5,6-三氯-2-吡啶基)磷酸及其二甲基类似物硫代磷酸O,O-二甲基-O-(3,5,6-三氯-2-吡啶基酯)在0.1 mM浓度下进行了测试。硫代磷酸O,O-二乙基-O-(3,5,6-三氯-2-吡啶基酯)使PAH分泌显著增加至对照的115%，而O,O-二乙基-O-(3,5,6-三氯-2-吡啶基)磷酸则抑制了28%。（摘要截于250字）
