Abstract

Incubation of renal cortex slices with 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) in vitro produced a marked enhancement in the formation of labeled cyclic adenosine 3',5'-monophosphate (cyclic AMP) from tritiated adenosine. Dose-response studies revealed that 10^-7 M p,p'-DDT was the minimal amount necessary to significantly raise renal cyclic AMP-³H formation whereas maximal stimulation was noted with 10^-6 M concentration of this insecticide. In addition, incubation of kidney cortex homogenates with p,p'-DDT (10^-6 M) produced a marked increase (192%) in the activity of adenyl cyclase. Administration of a single, oral dose of p,p'-DDT (600 mg/kg) significantly elevated (65%) the endogenous levels of cyclic AMP in the kidney cortex. p,p'-DDT treatment also enhanced the activity of both basal- (72%) and fluoride-stimulated (78%) forms of adenyl cyclase and produced a slight decrease in renal phosphodiesterase. Other organochlorine pesticides such as o, p'-DDT, α-chlordane, γ-chlordane, dieldrin, endrin, heptachlor and heptachlor epoxide seemed equally effective in elevating the in vitro formation of cyclic AMP-³H from tritiated adenosine. A similar enhancement in the synthesis of radioactive cyclic nucleotide was observed in liver slices incubated with p,p'-DDT. Caffeine, by itself, significantly increased renal cyclic AMP formation and when incubated simultaneously with p,p'-DDT, this methyl xanthine potentiated the action of the insecticide on cyclic AMP-³H synthesis. In contrast, the presence of imidazole reduced the p,p'-DDT-stimulated increase in the formation of cyclic AMP-³H by kidney cortex. Similarly, concurrent incubation with propranolol and p,p'-DDT resulted in a significant inhibition of the DDT-induced rise in cyclic AMP-³H production from tritiated adenosine. Hydrazine, an inhibitor of gluconeogenesis, also interfered with the ability of the pesticide to enhance cyclic AMP-³H formation by renal cortex slices. The enhancement in cyclic AMP-³H formation produced by p,p'-DDT was not affected when kidney cortices were incubated concurrently with this pesticide and either prostaglandin E₁ or F_2α. Our results demonstrate that p,p'-DDT is capable of increasing the formation of labeled cyclic AMP from tritiated adenosine in both kidney cortex and liver and suggest that the insecticide-induced changes in carbohydrate metabolism of these tissues may be associated with their ability to enhance the synthesis of cyclic AMP.