Impaired recovery of brain muscarinic receptor sites following an adaptive down-regulation induced by repeated administration of diisopropyl fluorophosphate in aged rats

Journal Article · Mon Jan 01 04:00:00 EST 1990 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(90)90027-O· OSTI ID:6970476

Pintor, A; Fortuna, S; De Angelis, S; Michalek, H ^[1]

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1. Istituto Superiore di Sanita, Rome (Italy)

Potential age-related differences in the recovery rate of brain cholinesterase activity (ChE) and muscarinic acetylcholine receptor binding sites (mAChRs) following reduction induced by repeated treatment with diisopropyl fluorophosphate (DFP) were evaluated in Sprague-Dawley rats. Male 3- and 24-month old rats were s.c. injected with DFP on alternate days for 2 weeks and killed 48 hr and 7, 14, 21, 28 and 35 days after the last treatment. In the hippocampus and striatum, but not in the cerebral cortex, of control rats there as a significant age-related decline of ChE activity and maximal density of 3H-QNB binding sites (Bmax). The repeated administration of DFP during the first week caused a syndrome of cholinergic stimulation both in aged and young rats. The syndrome was more pronounced, in terms of intensity and duration in aged than in young animals resulting in 40 and 12% mortality, respectively; during the second week the syndrome attenuated in the two age-groups. The percentage inhibition of brain ChE at the end of DFP treatment did not differ between young and surviving aged rats. The down-regulation of mACRs was present in the three brain regions of both young and age rats (from 20 to 40%). Factorial analysis of variance showed significant differences for age, recovery rate, and significant interaction between age and recovery rate, both for ChE and mAChRs in young rats the three brain areas.

• OSTI ID: 6970476
• Journal Information: Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 46:14; ISSN 0024-3205; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
AGE DEPENDENCE
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL RECOVERY
BODY
BRAIN
CARBOXYLESTERASES
CENTRAL NERVOUS SYSTEM
CHOLINESTERASE
DRUGS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
ESTERASES
ESTERS
HYDROGEN COMPOUNDS
HYDROLASES
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
RATS
REACTION KINETICS
RECEPTORS
RECOVERY
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES