Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90125-7· OSTI ID:6945480

Pintor, A; Fortuna, S; Volpe, M T; Michalek, H

Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of /sup 3/H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity.

• Research Organization: Istituto Superiore di Sanita, Rome (Italy)
• OSTI ID: 6945480
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 42:21; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AGE DEPENDENCE
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBOXYLESTERASES
CENTRAL NERVOUS SYSTEM
CHOLINESTERASE
DRUGS
ENZYME ACTIVITY
ENZYMES
ESTERASES
HYDROLASES
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHORUS COMPOUNDS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES