Effects of chronic lead exposure on glutamate release and uptake in cerebellar cells of rat pups.
Changes in the release and uptake of glutamate in cerebellar granule and glial cells of offspring of lead-exposed mothers were determined. In cultured cerebellar granule cells exposed to lead for 5 days, glutamate release was less influenced upon N-methyl-D-aspartate (NMDA) stimulation than that in the control. Although the NMDA-stimulated release of glutamate in cerebellar granule cells prepared from lead-exposed first generation pups was not different from that of the control group, the S-nitroso-N-acetylpenicillamine (SNAP)-stimulated release of glutamate in cerebellar granule cells obtained from lead-treated pups was less elevated than that in the control. Furthermore, in cerebellar granule cells obtained from lead-exposed second generations pups, glutamate release did not respond to both NMDA and SNAP stimulation. In cerebellar glial cells exposed to lead, the basal glutamate uptake was not changed. However, the L-trans-pyrollidine-2,4-dicarboxylic acid (PDC)-blocking effects was significantly reduced. In glial cells obtained from lead-exposed pups, the glutamate uptake was also less blocked by PDC than that in the control. Further decreases in PDC-blocking effects were observed in cerebellar glial cells obtained from lead-treated second generation pups compared to those from the control group. These results indicate that lead exposure induces the changes in the sensitivities of the glutamate release and uptake transporter. In addition, these results suggest that lead exposure might affect the intracellular signalling pathway and transmission in glutamatergic nervous system.
Yi
E Y
EY
College of Pharmacy, Chonnam National University, Kwangju, Korea.
Lim
D K
DK
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D007854:Lead / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007854:Lead; D018698:Glutamic Acid; D016202:N-Methylaspartate; D026423:S-Nitroso-N-Acetylpenicillamine; D000254:Sodium-Potassium-Exchanging ATPase; D010396:Penicillamine