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 a nion transport based on inhibition of the active transepithelial trans port of p-aminohippuric acid ([H-3]PAH) by primary cultures of winter flounder proximal tubules. Four structurally similar chlorophenoxy aci d herbicides were tested. 2-Methyl-4 chlorophenoxyacetic acid at 0.1 m M had no effect on PAH transport. 2-(2,4-Dichlorophenoxy)propionic aci d, 2-(2-methyl,4 chlorophenoxy)propionic acid and 2,4-dichlorophenoxya cetic 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 concentrati ons 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, phosp hothioic 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-trich-loro-2 -pyridinyl ester) increased PAH secretion significantly to 115% of con trol whereas the O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphate in hibited by 28%. The biphasic effects exhibited in the dose-response cu rves of several pesticides are similar to those noted with respect to a-ketoglutarate and may reflect time-dependent trans and cis interacti ons on the basolateral PAH:alpha-ketoglutarate anion exchanger.