EFFECTS OF PARAQUAT, DINOSEB AND 2,4-D ON INTRACELLULAR CALCIUM AND ON VASOPRESSIN-INDUCED CALCIUM MOBILIZATION IN ISOLATED HEPATOCYTES

The effects of the herbicides paraquat, dinoseb and 2,4-D on intracell ular Ca2+ levels and on vasopressin-induced Ca2+ mobilization were inv estigated in intact isolated hepatocytes. Incubation of rat hepatocyte s with paraquat (5 mM for 60 min) and dinoseb (10 mu M) resulted in a time-dependent loss of viability by approximately 25%. Viability of ce lls treated with 2,4-D decreased significantly, dropping to about 20% at 10 mM and 60 min incubation. Exposure of hepatocytes to paraquat (1 -10 mM) for 60 min had no effect on the basal level of [Ca2+](i). Addi tionally, exposure to paraquat had no effect on the magnitude and on t he duration of the [Ca2+](i) response to vasopressin. In the presence of 2,4-D (1-10 mM), basal [Ca2+](i) increases as a function of herbici de concentration. The magnitude of the [Ca2+](i) response decreases fr om 256 +/- 8 nM in control to 220 +/- 5 nM, at 10 mM 2,4-D. Exposure o f hepatocytes to dinoseb (1-10 mu M) had no effect on the basal level of [Ca2+](i). However, a strong concentration-dependent decrease in th e magnitude of Delta[Ca2+](i) in response to vasopressin was noticed a t 60 min incubation. Dinoseb markedly inhibited the stimulation of the production of inositol phosphates by vasopressin stimulus. The presen t study demonstrates that paraquat, 2,4-D and dinoseb cause cell death in hepatocytes by mechanisms not related to an early increase in [Ca2 +](i). Additionally, it has been shown for the first time that dinoseb disturbs the transduction mechanism promoted by vasopressin by inhibi ting the formation of IP3.