The effects of aluminum on agonist-induced alterations in cyclic AMP and cyclic GMP concentrations in rat brain regions in vivo.
Aluminum administered intracerebroventricularly (icv) (1 mumol) caused a significant decrease in cyclic GMP in the cortex after 3 days and a significant increase in cyclic AMP in the cortex after 14 days. Pilocarpine administration to untreated rats elevated cyclic AMP and cyclic GMP levels in specific brain regions. These pilocarpine-induced increases in the cyclic nucleotide concentrations were significantly attenuated in rats that had been treated with aluminum 14 days previously. Isoproterenol administration to control rats did not alter cyclic AMP concentrations; however, cyclic AMP concentrations were significantly reduced in the cortex of aluminum-treated animals after isoproterenol administration. Apomorphine elevated cyclic GMP concentrations in the cerebellum, hippocampus, and striatum of naive rats. This apomorphine-induced elevation in cyclic GMP concentrations was significantly potentiated in aluminum-treated rats. These results indicate that: (1) cyclic AMP synthesis in the cortex is most sensitive to aluminum; (2) agonist-stimulated changes in cyclic nucleotide concentrations can be altered by pretreatment with aluminum; (3) effects of aluminum persist for at least 2 weeks after central administration; and (4) modulation of the metabolism of cyclic nucleotides may play a role in the neurotoxic effects of aluminum.
Johnson
G V
GV
Department of Pharmacology, University of Alabama, Birmingham 35294.
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004347:Drug Interactions; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010862:Pilocarpine; D000535:Aluminum; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D001058:Apomorphine