Vesicular Catecholamine Release from Rat PC12 Cells on Acute and Subchronic Exposure to Polychlorinated Biphenyls

Abstract

Key Words: PCB; quantal catecholamine release; rat PC12 phaeochromocytoma cells; carbon fiber microelectrode amperometry.The neurotoxic potential of specific polychlorinated biphenyls (PCBs) and related substances, many of which persist in the environment and may accumulate in biological tissues, is a matter of toxicological concern (Tilson and . Behavioral symptoms and brain neurotransmitter levels in exposed animals, as well as in vitro experimental data, indicate involvement of monoaminergic systems in PCB neurotoxicity and of the dopaminergic system in particular (for review see Seegal, 1995).Potential mechanisms underlying the effects of PCBs on the catecholaminergic system have been addressed using in vitro model systems. Several of the ortho-substituted, nonplanar PCB congeners reduce the dopamine contents of rat phaeochromocytoma (PC12) cells after 6 h of exposure with IC50 values Ͻ 100 M, whereas coplanar congeners are inactive in this respect . In an additional study of PC12 cells, the threshold concentrations of several PCB congeners to affect cellular dopamine contents and basal and evoked dopamine release were reported to be close to 10 M (Angus and Contreras, 1996). In primary cultured bovine adrenal chromaffin cells, exposed to 50 -100 M of the nonplanar congener 2,2Ј,4,4Ј-tetrachlorobiphenyl for 1 and 5 days, cellular catecholamine contents and evoked catecholamine release were reduced, and basal catecholamine release was enhanced. The coplanar congener 3,3Ј,4,4Ј-tetrachlorobiphenyl did not cause any of these effects at concentrations up to 100 M (Messeri et al., 1997).Experiments with rat PC12 and mouse neuroblastoma N1E-115 cells have shown that 30 -200 M 2,2Ј-dichlorobiphenyl (PCB 4) inhibits tyrosine hydroxylase. A less potent, partial inhibition of tyrosine hydroxylase activity by PCB 4 was observed in minced rat corpus striatum (Choksi et al., 1997). Uptake of dopamine into rat brain synaptosomes and into rat brain synaptic vesicles are both inhibited by micromolar concentrations of PCBs. Highly chlorinated congeners appear to inhibit the plasma membrane dopamine transporter more potently than the vesicular monoamine transporter (Mariussen et al., 1999;Mariussen and Fonnum, 2001). Exposure of primary cultured rat neocortical and cerebellar granule cells to micromolar concentrations of PCBs may lead to variety of early transient, sustained, and oscillatory elevations of the intracellular Ca 2ϩ concentration (Kodavanti et al., 1993;Carpenter et al., 1997;Mundy et al., 1999;Inglefield and Shafer, 2000;Inglefield et al., 2001). Elevation of the intracellular Ca 2ϩ concentration and of Ca 2ϩ /calmodulin-dependent protein kinase II (CaM kinase II) activation, i.e., common intracellular signaling pathways, appear to be involved in PCB-induced release of insulin from RINm5F rat insuloma cells (Fischer et al., 1996(Fischer et al., , 1999 to cause an elevation of the intracellular Ca 2ϩ concentration (Wong et al., 2001). Several of the alleged mechanisms of action of PCBs would be expected to lead t...

Bromophenols, both present in marine organisms and in industrial flame retardants, disturb cellular Ca2+ signaling in neuroendocrine cells (PC12)

“…We chose the rat cell line PC12 from a phaeochromocytoma of the adrenal gland, which produces and secretes noradrenalin as well as dopamine (Greene and Tischler, 1976). Cells of the adrenal gland have been used previously for many toxicological and pharmacological studies, e.g., PCBs (Messeri et al, 1997;Westerink and Vijverberg, 2002a) heavy metals (Weinsberg et al, 1995;Westerink and Vijverberg, 2002b) and alkaloids (Lee and Kim, 1996;Gafni et al, 1997;Bickmeyer et al, 1998Bickmeyer et al, , 2004Kim et al, 2001;Smith et al, 2002). The aim of the present study was to investigate the interactions of naturally as well as industrially important chemicals, which are suspected to interact with the humoral system (Legler and Brouwer, 2003), with cellular signaling.…”

The marine secondary metabolites 2,4-dibromophenol and 2,4,6-tribromophenol differentially modulate voltage dependent ion currents in neuroendocrine (PC12) cells

“…PCBs (Messeri et al, 1997;Westerink and Vijverberg, 2002a) heavy metals (Shafer and Atchison, 1991;Weinsberg et al, 1995;Westerink and Vijverberg, 2002b) and alkaloids (Lee and Kim, 1996;Gafni et al, 1997;Bickmeyer et al, 1998;Kim et al, 2001;Smith et al, 2002;Bickmeyer et al, 2004). We chose the rat cell line PC12 from a phaeochromocytoma of the adrenal gland, which produces and secretes noradrenalin as well as dopamine (Greene and Tischler, 1976).…”

A secondary metabolite, 4,5-dibromopyrrole-2-carboxylic acid, from marine sponges of the genus Agelas alters cellular calcium signals

“…These cells can be differentiated into neuron-like cells and produce catecholamines as adrenalin, noradrenalin and dopamine like their organ counterpart, the chromaffin cells from the adrenal gland. Chromaffin cells and PC12 cells have been widely used for pharmacological and toxicological investigations of heavy metals (Weinsberg et al, 1995;Westerink and Vijverberg, 2002a), polychlorinated biphenyls (Messeri et al, 1997;Westerink and Vijverberg, 2002b) and alkaloids (Lee and Kim, 1996;Gafni et al, 1997;Bickmeyer et al, 1998;Kim et al, 2001;Smith et al, 2002). Hormone secretion is triggered by influx of extracellular calcium through voltage dependent calcium channels, which can be monitored using calcium sensitive dyes (Grynkiewicz et al, 1985;Deitmer and Schild, 2000).…”