Age-dependent neurotoxicity in rats chronically exposed to low levels of lead: calcium homeostasis in central neurons.
Chronic exposure of rats to low level (1 mg/kg. day) lead ingestion starting at a prenatal age reduced the number of IP3 receptors in ER and reduced the capacity of IP3 to increase Cai2+ in permeabilized neurons obtained from the cerebral cortices. Chronic exposure of adult rats to a comparable dose of lead did not cause these changes. A second stimulation of samples with IP3 in the absence of extracellular Ca2+ did not further increase Cai2+ suggesting the depletion of the IP3 sensitive Ca2+ pool. However, when IP4 preceded the second IP3 stimulation, an increase in Cai2+ was noted. In samples exposed to La3+ followed by IP3, Cai2+ remained elevated and did not return to the base line which suggests that the IP3 sensitive pool of Ca2+ is removed from neurons primarily by active extrusion. When IP4 was added to the samples exposed to La3+ and IP3, a significant decrease in Cai2+ was noted. These observations suggest that IP4 refills Ca2+ stores possibly by redistributing Ca2+ from cytoplasm to the stores. Chronic low level lead ingestion starting prenatally or at an adult age did not impair the effect of IP4 on Cai2+ suggesting that the IP4 induced redistribution of Ca2+ from cytoplasm to intracellular Ca2+ stores is not effected by chronic exposure of rats to low level lead ingestion. The present observations that chronic exposure of rats to low level lead ingestion does not effect the capacity of GTP to increase Cai2+ but attenuated the combined effects of GTP and IP3 in neurons further suggest that IP3 receptors are specifically down-regulated by prenatal lead exposure.
Singh
A K
AK
Department of Veterinary Diagnostic Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007700:Kinetics; D007855:Lead Poisoning / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013997:Time Factors
D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium