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Title: Action of AF64A on rat brain muscarinic receptors

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:
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
Research Org:
Fidia-Georgetown Institute for the Neurosciences, Washington, DC
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