The effect of polychlorinated biphenyls on the high affinity uptake of theneurotransmitters, dopamine, serotonin, glutamate and GABA, into rat brainsynaptosomes

Studies have shown that polychlorinated biphenyls (PCB) may affect cognitiv e functions both in human and also in experimental animals. We have investi gated whether this effect could be caused by an inhibition of the uptake of selected neurotransmitters into rat brain synaptosomes. Ortho-chlorinated biphenyls were found to inhibit transmitter transport into synaptosomes fro m rat brain. In contrast, several nonortho-chlorinated biphenyls did not in hibit uptake. The uptake of dopamine, glutamate, GABA and serotonin was inh ibited by the PCB mixtures, Aroclor 1242 and 1254. Under identical conditio n, the uptake of dopamine was inhibited more efficient than that of glutama te. The inhibition of neurotransmitter uptake was found to be dependent on the chlorination patterns of the PCB congeners, (i) ortho-chlorinated PCBs with four to five chlorine substituents (with the exception of 2,2',6,6'-Te CB) were the most effective inhibitors; (ii) hexa- or heptachlorinated PCBs were poor inhibitors or partial inhibitors (e.g. 2,2',4,4',5,5' HCB) of gl utamate and GABA uptake. Kinetic studies indicated that Aroclor 1242 inhibi ted dopamine uptake mainly competitively. The uptake of glutamate and GABA was inhibited in either a mixed competitive or in a non-competitive way, re spectively. The neurotoxic concequences of the effect of different PCBs on neurotransmitter uptake on the uptake into synaptosomes are discussed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.