In vivo effects of cadmium on calmodulin and calmodulin regulated enzymes in rat brain.
Effect of chronic cadmium (Cd) exposure and the influence of diethyldithiocarbamate (DDC) on Cd absorption was studied on the brain of young male Wistar rats. A significant amount of Cd accumulated in cerebral cortices of rats after 4 weeks of Cd (6 mg/kg body wt) exposure (through gastric intubation). The biological activity of calmodulin (CaM) decreased significantly (p less than 0.001) in the cerebral cortices of these animals in comparison to the control group. 3'-5' Phosphodiesterase and synaptic membrane Ca(2+)-Mg(2+) ATPase were also significantly affected (p less than 0.01 and p less than 0.001 respectively). However, Cd treatment did not alter synaptic membrane adenylate cyclase activity and DDC (9.2 mg/kg body wt, intraperitoneal) treatment along with Cd (6 mg/kg body wt) enhanced Cd accumulation in cerebral cortices of treated animals resulting in an increased inhibition of CaM and CaM dependent enzymes. These data suggest that Cd may be acting via binding to CaM and uncoupling it from its normal cellular control of calcium.
Vig
P J
PJ
Department of Neurology, University of Mississippi Medical Center, Jackson 39216.
Nath
R
R
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004050:Ditiocarb / Q000633:toxicity; D008297:Male; D010726:Phosphodiesterase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D000067956:Adenylyl Cyclase Inhibitors; D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D002104:Cadmium; D004050:Ditiocarb; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases