NDLI: Nicotinic Receptor Inhibition by Tetraponera Ant Alkaloids

Content Provider	Springer Nature Link
Author	Kem, William R. Wildeboer, Kristin LeFrancois, Susan Raja, Ma'an Marszalec, William Braekman, Jean Claude
Copyright Year	2004
Abstract	1. Tetraponerines are a group of alkaloids occurring in the venoms of ants belonging to the genus Tetraponera. Eight compounds had been isolated and their structures elucidated, but their mechanisms of action had not yet been reported. We have studied the actions of several of these tetraponerines on vertebrate neuromuscular, ganglionic, and brain nicotinic acetylcholine receptors (nAChRs) using a variety of techniques including muscle contracture, cultured cell functional assays, neuronal patch clamping, and radioligand binding methods.2. Potency for inhibition of the frog muscle carbachol-elicited contracture increased as the carbon 9 side chain alkyl group was increased in length to 10–12 carbons, then decreased when the chain was 18-carbons long. Potency differences between T-7 and T-8, which differ only in the stereochemistry of the carbon pentyl side chain were rather small. Quaternization of either N atom in a T-8 analog bearing a 10-carbon length alkyl substituent did not greatly affect potency for inhibition of the muscle response; thus the ionized form is an active form of this tetraponerine.3. T-7 inhibited the nicotine-stimulated efflux of 86Rb from cultured PC12 cells, which primarily express alpha3–beta4 ganglionic type nicotinic receptors. T-8 blockade of BTX-sensitive and insensitive neuronal nAChRs, as studied by patchclamp recordings from cultured rat brain neurons, was also consistent with a noncompetitive type of inhibition.4. T-7 displaced binding of the nAChR ion channel binding ligand thienylcyclophenidyl (TCP), an analog of PCP, to Torpedo neuromuscular type receptors. The affinity of the TCP binding site for T-7 did not depend upon the desensitization state of the receptor.5. We conclude that the tetraponerines act at a site on nAChRs different from the ACh binding site which is probably located within the ion channel.
Starting Page	535
Ending Page	551
Page Count	17
File Format	PDF
ISSN	02724340
Journal	Cellular and Molecular Neurobiology
Volume Number	24
Issue Number	4
e-ISSN	15736830
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2004-01-01
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	Neurosciences Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Cellular and Molecular Neuroscience

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