title: Interaction of structurally similar pesticides with organic anion transport by primary cultures of winter flounder renal proximal tubule.
abstract: 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)
authors.affiliation: Marine/Freshwater Biomedical Sciences Center, University of Connecticut, Storrs.
authors.forename: M A
authors.initials: MA
authors.lastname: Dawson
authors.forename: J L
authors.initials: JL
authors.lastname: Renfro
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity; D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004390:Chlorpyrifos / Q000494:pharmacology; D046508:Culture Techniques; D003634:DDT / Q000031:analogs & derivatives / Q000633:toxicity; D005432:Flounder; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
chemical_list: D010575:Pesticides; D015084:2,4-Dichlorophenoxyacetic Acid; C008340:mecoprop; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D008456:2-Methyl-4-chlorophenoxyacetic Acid; D004390:Chlorpyrifos; D010130:p-Aminohippuric Acid