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Title: Action of AF64A on rat brain muscarinic receptors

Abstract

ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased but its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.

Authors:
;
Publication Date:
Research Org.:
Fidia-Georgetown Institute for the Neurosciences, Washington, DC
OSTI Identifier:
5463250
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA; TRN: 86-028336
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; RECEPTORS; BIOCHEMICAL REACTION KINETICS; SYMPATHOLYTICS; BRAIN; CHOLINE; CYCLASES; DOSE-RESPONSE RELATIONSHIPS; HIPPOCAMPUS; INOSITOL; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ALCOHOLS; AMINES; AMMONIUM COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARBOHYDRATES; CENTRAL NERVOUS SYSTEM; DRUGS; ENZYMES; HYDROXY COMPOUNDS; INOSITOLS; ISOTOPE APPLICATIONS; KINETICS; LABELLED COMPOUNDS; LIPOTROPIC FACTORS; LYASES; MAMMALS; MEMBRANE PROTEINS; MONOSACCHARIDES; NERVOUS SYSTEM; ORGANIC COMPOUNDS; ORGANS; PROTEINS; QUATERNARY COMPOUNDS; REACTION KINETICS; RODENTS; SACCHARIDES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Eva, C., and Costa, E.. Action of AF64A on rat brain muscarinic receptors. United States: N. p., 1986. Web.
Eva, C., & Costa, E.. Action of AF64A on rat brain muscarinic receptors. United States.
Eva, C., and Costa, E.. 1986. "Action of AF64A on rat brain muscarinic receptors". United States. doi:.
@article{osti_5463250,
title = {Action of AF64A on rat brain muscarinic receptors},
author = {Eva, C. and Costa, E.},
abstractNote = {ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased but its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:3,
place = {United States},
year = 1986,
month = 3
}

Conference:
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  • Several acetylcholinesterase (AChE) inhibitors decrease muscarinic cholinergic (mACh) receptors in the brain, alteration of dopamine (DA) and ..gamma..-aminobutyric acid (GABA) receptors after AChE inhibition was also reported. In view of the important interactions among DA, GABA and ACh systems, whether this is a common effect of AChE inhibitors should be established. They report the effect of the AChE inhibitor, paraoxon, on DA, GABA and mACh receptors in the rat. The binding of /sup 3/H-QNB (for mACh), /sup 3/H-spiperone (for DA) and /sup 3/H-muscimol (for GABA) to striatal and hippocampal membranes was analyzed. Also, behavioral sensitivity to atropine was studied. Twenty-fourmore » hr after a single dose (0.75 mg/kg, s.c.) of paraoxon, the density of mACh receptors in the striatum was decreased but, at 3 days, no change was seen. In the hippocampus, the mACh receptors were not affected. Repeated treatment with paraoxon (0.3 mg/kg, 48 hourly) for 2 weeks reduced the mACh receptor density in both regions. Neither single nor repeated paraoxon treatment had an effect on DA or GABA receptors. After single or repeated dosing with paraoxon, myoclonus induced by atropine (10 mg/kg, i.p.) was enhanced. The results show rapid downregulation of mACh receptors by paraoxon. DA or GABA, however, appear not to be affected under these treatment regimens.« less
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