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DIFFERENTIAL EFFECTS OF POLYCHLORINATED BIPHENYL CONGENERS ON PHOSPHOINOSITIDE HYDROLYSIS AND PROTEIN KINASE C TRANSLOCATION IN RAT CEREBELLAR GRANULE CELLS
Citation:
Kodavanti, P., T. Shafer, T. Ward, W. Mundy, T. Freudenrich, G. Harry, AND H. Tilson. DIFFERENTIAL EFFECTS OF POLYCHLORINATED BIPHENYL CONGENERS ON PHOSPHOINOSITIDE HYDROLYSIS AND PROTEIN KINASE C TRANSLOCATION IN RAT CEREBELLAR GRANULE CELLS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/051.
Description:
Previous reports from our laboratory have suggested that the neuroactivity of some polychlorinated biphenyl (PCB) congeners is associated with perturbations in cellular Ca2+-homeostasis. o characterize the neurochemical effects of PCBs further, the present experiments found that neither 2,21-dichlorobiphenyl (DCBP), an orthosubstituted congener, nor 3,3',4,41,5-pentachlorobiphenyl (PCBP), a non orthosubstitutel congener, affected basal phosphoinositide (PI) hydrolysis in cerebellar granule cells. owever, at concentrations up to 50 uM, DCBP potentiated carbachol-stimulated PI hydrolysis, while decreasing it at 100 uM. CBP, on the other hand, had no effect on carbachol/stimulated PI hydrolysis in concentrations up-to 100 uM. Using [3H]-phorbol ester ([3h]PDBu) binding as an estimate of protein kinase C (PKC) activation/trans-location, DCBP increased [3H]PDBu binding at concentrations up to 100 uM. he effect of DCBP on [3H]PDBu binding was timed-dependent, and also dependent on the presence of external Ca2+ in the medium. oth PCBs were observed to increase cerebellar granule cells. o test the hypothesis that DCBP may increase 45Ca2+-influx and increase [3H]PDBu binding by acting on receptor activated calcium channels, the effects of DCBP were compared to those of L-glutamate. he effects of DCBP and glutamate were additive. K-801, a non-competitive NMDA antagonist, blocked the effects of glutamate, while having no effect on DCBP-induced increase in [3H]PDBu binding. ther pharmacological pretreatments such as incubations with 3-(2-carboxypiperazin-4-yl)