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 intracellular Ca2+ levels and on vasopressin-induced Ca2+ mobilization were investigated in intact isolated hepatocytes. Incubation of rat hepatocytes with paraquat (5 mM for 60 min) and dinoseb (10 microM) resulted in a time-dependent loss of viability by approximately 25%. Viability of cells 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. Additionally, exposure to paraquat had no effect on the magnitude and on the 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 herbicide concentration. The magnitude of the delta[Ca2+]i response decreases from 256 +/- 8 nM in control to 220 +/- 5 nM, at 10 mM 2,4-D. Exposure of hepatocytes to dinoseb (1-10 microM) had no effect on the basal level of [Ca2+]i. However, a strong concentration-dependent decrease in the magnitude of delta[Ca2+]i in response to vasopressin was noticed at 60 min incubation. Dinoseb markedly inhibited the stimulation of the production of inositol phosphates by vasopressin stimulus. The present 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 inhibiting the formation of IP3.
Palmeira
C M
CM
Department of Zoology, University of Coimbra, Portugal.
Moreno
A J
AJ
Madeira
V M
VM
D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity; D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002852:Chromatography, Ion Exchange; D004396:Coloring Agents / Q000737:chemistry; D004140:Dinitrophenols / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000633:toxicity*; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010269:Paraquat / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014343:Trypan Blue / Q000737:chemistry; D014667:Vasopressins / Q000494:pharmacology
D004396:Coloring Agents; D004140:Dinitrophenols; D006540:Herbicides; D007295:Inositol Phosphates; D014667:Vasopressins; D015084:2,4-Dichlorophenoxyacetic Acid; D014343:Trypan Blue; D010269:Paraquat; D019297:2,4-Dinitrophenol; D002118:Calcium; C018527:dinoseb