Interaction of structurally similar pesticides with organic anion transport by primary cultures of winter flounder renal proximal tubule.
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)
Dawson
M A
MA
Marine/Freshwater Biomedical Sciences Center, University of Connecticut, Storrs.
Renfro
J L
JL
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
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