Responses to N-methyl-D-aspartate and kainic acid in cerebellar granule cells of lead-exposed rat pups.
To determine changes in response to N-methyl-D-aspartate (NMDA) and kainic acid (KA) in cerebellar granule cells of offspring of lead-exposed mothers, pregnant rats received 0.25% lead acetate in their drinking water 2 days after mating. The control animals were given sodium acetate (0.125%) in their drinking water. The cerebellar granule cells were cultured from 8-day old pups. Changes in the levels of cytosolic Ca++ and cGMP and the release of glutamic acid were measured using fura-2 spectrofluorometer, radio-immunoassay, and HPLC, respectively. Increases in cytosolic Ca++ in response to 50 microM of NMDA and KA were less responsive (77%) in the lead exposed group as compared to that of the control group. However, the maximum responses to KA were not different. The NMDA- and KA-stimulated release of glutamate from cerebellar granule cells prepared from lead-exposed pups were also significantly reduced. While the NMDA-induced elevation of cGMP was not affected in the lead-exposed pups, the normal KA-induced increases in cGMP level in cerebellar granule cells of lead-exposed pups was not observed. The specific binding of [3H]MK-801 was significantly lower in cerebellar granule cells of the lead-exposed pups. These results indicate that lead exposure to the mother affects excitatory amino acid systems during the development of the offspring.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
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D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology*; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D016202:N-Methylaspartate / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats
D007854:Lead; D016202:N-Methylaspartate; D007608:Kainic Acid