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Dawson MA, Renfro JL: Interaction of structurally similar pesticides with organic anion transport by primary cultures of winter flounder renal proximal tubule. 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) |
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