Effect of chronic lead ingestion by rats on glucose metabolism and acetylcholine synthesis in cerebral cortex slices.
The effect of chronic low-level lead (Pb2+) ingestion on the metabolic pathways leading to the acetyl moiety of acetylcholine (ACh) was examined. Cerebral cortex slices, prepared from untreated or Pb2+-exposed rats (600 ppm lead acetate in the drinking water for 20 days), were incubated in Krebs-Ringer bicarbonate buffer with 10 mM glucose and tracer amounts of [6-3H]glucose and either [6-14C]glucose or [3-14C] beta-hydroxybutyrate. Altering the concentration of Pb2+ in the drinking water produced a dose-related increase in blood and brain lead levels. When tissue from Pb2+-exposed rats was incubated with mixed-label glucose, incorporation into lacate, citrate, and ACh was considerably decreased, although no changes occurred in the 3H/14C rations. Similar effects of Pb2+ were found when 14C-labeled beta-hydroxybutyrate was substituted for the [14C]glucose. It appears from these data that Pb2+ exerts a generalized effect on energy metabolism and not on a specific step in glucose metabolism. The impairment of glucose metabolism may explain partially the Pb2+-induced changes observed in cholinergic function.
D020155:3-Hydroxybutyric Acid; D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism; D007854:Lead / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006885:Hydroxybutyrates; D007854:Lead; D005947:Glucose; D000109:Acetylcholine; D020155:3-Hydroxybutyric Acid