The effect of polychlorinated biphenyls on the uptake of dopamine and other neurotransmitters into rat brain synaptic vesicles

Studies have shown that polychlorinated biphenyls may affect cognitive func tions both in human and also in experimental animals. One of the neurochemi cal parameters that is changed after exposure to these compounds is a reduc tion in the dopamine level in the brain, although the mechanism behind this reduction is not known. We have therefore investigated whether this reduct ion could be caused by an effect on vesicular uptake. ortho-Chlorinated bip henyls are found to be competitive inhibitors of dopamine transport into sy naptic vesicles from rat brain with K-i concentrations as low as 4 mu M. In contrast, several nonortho-chlorinated biphenyls did not inhibit vesicular uptake. The inhibition was specific for dopamine, in that the uptake of gl utamate and GABA was inhibited at higher PCB concentrations under identical conditions. The vesicular Mg-ATPase proton pump was also inhibited at high er concentrations of PCBs than the dopamine transport. Uptake of methylamin e gave no indication of any disruption of the vesicular proton gradient. Th e inhibition of dopamine vesicular uptake by PCBs was competitive. Several of the ortho-PCBs also inhibited the binding of tetrabenazine, which is kno wn to bind to a site close to the dopamine binding site, at the vesicular t ransporter. The results show that inhibition of vesicular uptake may contri bute to the decrease of dopamine reported in nervous tissue after exposure to PCBs under different conditions. (C) 1999 Academic Press.