title: Effects of extracellular acetylcholine on muscarinic receptor binding assessed by [125I]dexetimide and a simple probe.
abstract: New pharmacologic approaches to enhance brain cholinergic function focus on increasing intrasynaptic acetylcholine. We examined the usefulness of a simple probe and [125I]dexetimide to evaluate in vivo the effects of extracellular acetylcholine on muscarinic receptor binding in the mouse brain. After radiotracer injection continuous time/activity curves were generated over 330 min. [125I]Dexetimide reached a plateau at 90 min post-injection. To increase extracellular acetylcholine, the anticholinesterase physostigmine was administered at 120 min, producing a reversible decrease in [125I]dexetimide specific binding (23%) for 30 min. These findings demonstrate that dynamic changes in extracellular acetylcholine can be evaluated by displacement of [125I]dexetimide binding in vivo using a simple probe system.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD 21205-2179, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Sánchez-Roa
authors.forename: H N
authors.initials: HN
authors.lastname: Wagner
authors.forename: V L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: E D
authors.initials: ED
authors.lastname: London
authors.forename: J R
authors.initials: JR
authors.lastname: Lever
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003909:Dexetimide / Q000378:metabolism* / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D015902:Gamma Cameras; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000378:metabolism* / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011877:Radionuclide Imaging; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; C018580:levetimide; D003909:Dexetimide; D010830:Physostigmine; D000109:Acetylcholine