Amyloid-beta production in aged guinea pigs: atropine-induced enhancement is reversed by naloxone.
Advanced age, cholinergic deficit, and elevated brain levels of enkephalin are associated with sporadic Alzheimer's disease. The influence of these factors on production of amyloidogenic peptides (Abeta) is uncertain. In the present experiments, the levels of 40/42 amino acid-residue Abeta were measured in the brain cortex of guinea pigs aged 15-16 weeks (young) and 25-26 months (aged). As was found, injections of atropine (21 days, 5mg/kg/day) increase Abeta levels in aged but not young animals. This atropine-induced effect was antagonized by simultaneous injections of naloxone (3mg/kg/day) whereas naloxone alone failed to affect Abeta accumulation. These results are discussed in the light of a possible "acetylcholine - Abeta" feedback loop and an influence of enkephalin on the loop function.
Ionov
Ilya D
ID
Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Leninsky Prospect 123-4-63, Moscow 117513, Russia. canyon1@rol.ru
Pushinskaya
Irina I
II
D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists
D016229:Amyloid beta-Peptides; D004745:Enkephalins; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D009270:Naloxone; D001285:Atropine