Responsiveness of brain muscarinic acetylcholine receptors in aged rats.
In the first part of the investigation the age-related changes in cortical, hippocampal and striatal cholinesterases (ChE), choline acetyltransferase (ChAT) and muscarinic acetylcholine receptors (mAChRs, measured as Bmax of 3H-QNB binding) were compared in male Wistar, Fischer 344 and Sprague-Dawley rats aged 3 and 24 months. Fischer rats exhibited 1.5 fold higher levels of ChAT and mAChRs than Wistar and Sprague-Dawley rats in the areas analyzed. The age-related decline of cortical ChAT and mAChRs was present in Fischer rats but not in those of the other two strains, i.e. was strain-dependent. There were no age-related changes in hippocampal ChAT in any strain. The decline of striatal ChAT, hippocampal and striatal mAChRs and ChE in the three regions analyzed were present in Wistar, Fischer and Sprague-Dawley aged rats. Thus, these deficits (or lack of changes) appeared to be not strain-dependent. The overall data indicate the importance of genotype in the rate of aging, and an accelerated aging for Fischer 344 rats. In the second part of the investigation the responsiveness of cortical mAChRs, ChE and ChAT to a repeated treatment with an indirect cholinergic agonist (an antiChE agent, diisopropyl fluorophosphate-DFP) was studied in two independent experiments on Fischer 344 and Sprague Dawley rats aged 3 and 24 months. The s.c. administration of DFP (first dose 1.6, subsequent six doses of 1.1 mg/kg on alternate days) to senescent Fischer rats caused a considerably more pronounced syndrome of cholinergic stimulation than in young ones, resulting in 60 and 14% mortality, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Michalek
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H
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Rome, Italy.
Pintor
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A
Fortuna
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D015536:Down-Regulation; D007531:Isoflurophate / Q000633:toxicity; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344 / Q000235:genetics / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000235:genetics / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D007531:Isoflurophate; D002795:Choline O-Acetyltransferase; D002802:Cholinesterases