Systemic administration of lithium chloride and tacrine increases nitric oxide synthase activity in the hippocampus of rats.
We planned to ascertain whether the administration of the anticholinesterase, tacrine (5 mg/kg i.p.), to rats pretreated 24 h before with lithium chloride (LiCl; 12 mEq/kg i.p.) produced any change in nitric oxide (NO) synthase activity in the hippocampus. A significant increase in hippocampal Ca(2+)-calmodulin-dependent NO synthase activity occurred 15 min after tacrine injection and was blocked by atropine (5 mg/kg i.p. given 15 min before tacrine) and by N omega-nitro-L-arginine methyl ester (300 micrograms given into one lateral cerebral ventricle 10 min before tacrine), a NO synthase inhibitor. A consistent cyclic guanosine 3',5'-monophosphate (cGMP) accumulation was also seen. In conclusion, the present results show that tacrine given to LiCl-pretreated rats produces a significant increase in NO synthase activity in the hippocampus and this may be responsible, at least in part, for seizures and related brain damage elicited by these drugs.
Bagetta
G
G
Department of Biology, University of Rome Tor Vergata, Italy.
Massoud
R
R
Rodinò
P
P
Federici
G
G
Nisticò
G
G
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced; D013619:Tacrine / Q000494:pharmacology*
D002712:Chlorides; D013619:Tacrine; D001285:Atropine; D001120:Arginine; D008094:Lithium; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D018021:Lithium Chloride; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester