The effect of polychlorinated biphenyls on the high affinity uptake of the neurotransmitters, dopamine, serotonin, glutamate and GABA, into rat brain synaptosomes.
Studies have shown that polychlorinated biphenyls (PCB) may affect cognitive functions both in human and also in experimental animals. We have investigated 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 from rat brain. In contrast, several nonortho-chlorinated biphenyls did not inhibit uptake. The uptake of dopamine, glutamate, GABA and serotonin was inhibited by the PCB mixtures, Aroclor 1242 and 1254. Under identical condition, the uptake of dopamine was inhibited more efficient than that of glutamate. 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'-TeCB) 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 glutamate and GABA uptake. Kinetic studies indicated that Aroclor 1242 inhibited dopamine uptake mainly competitively. The uptake of glutamate and GABA was inhibited in either a mixed competitive or in a non-competitive way, respectively. The neurotoxic consequences of the effect of different PCBs on neurotransmitter uptake on the uptake into synaptosomes are discussed.
Division for Protection and Materiel, Norwegian Defence Research Establishment, PO Box 25, 2027, Kjeller, Norway. espen.mariussen@ffi.no
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D000818:Animals; D001140:Aroclors / Q000737:chemistry / Q000633:toxicity; D001923:Brain Chemistry / Q000187:drug effects*; D020111:Chlorodiphenyl (54% Chlorine) / Q000737:chemistry / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001140:Aroclors; D018377:Neurotransmitter Agents; D020111:Chlorodiphenyl (54% Chlorine); D012701:Serotonin; D018698:Glutamic Acid; C027423:aroclor 1242; D005680:gamma-Aminobutyric Acid; D011078:Polychlorinated Biphenyls; D004298:Dopamine