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Action of nereistoxin on recombinant neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes
Authors:Valérie?Raymond Delpech,Makoto?Ihara,Claudio?Coddou,Kazuhiko?Matsuda,David?B.?Sattelle  author-information"  >  author-information__contact u-icon-before"  >  mailto:david.sattelle@anat.ox.ac.uk"   title="  david.sattelle@anat.ox.ac.uk"   itemprop="  email"   data-track="  click"   data-track-action="  Email author"   data-track-label="  "  >Email author
Affiliation:(1) MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK;(2) Department of Agricultural Chemistry, Faculty of Agriculture, Kinki University, 3327-204 Nakamachi, 631-8505 Nara, Japan;(3) Centro de Regulacion Celular y Patalogia, Instituto Milenio MIFAB, Unidad de Regulacion Neurohumoral, Departamento de Ciencias Fisiologicas, P. Universidad Catolica de Chile, 114-D Casilla, Santiago, Chile;(4) Present address: Centre de Recherches sur la Cognition Animale, UMR 5169, Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse Cedex, France
Abstract:Nereistoxin (NTX), a natural neurotoxin from the salivary glands of the marine annelid worm Lumbriconereis heteropoda, is highly toxic to insects. Its synthetic analogue, Cartap, was the first commercial insecticide based on a natural product. We have used voltage-clamp electrophysiology to compare the actions of NTX on recombinant nicotinic acetylcholine receptors (nicotinic AChRs) expressed in Xenopus laevis oocytes following nuclear injection of cDNAs. The recombinant nicotinic AChRs investigated were chicken agr7, chicken agr4beta2 and the Drosophila melanogaster/chicken hybrid receptors SAD/beta2 and ALS/beta2. No agonist action of NTX (0.1–100 mgrM) was observed on chicken agr7, chicken agr4beta2 and the Drosophila/chicken hybrid nicotinic AChRs. Currents elicited by ACh were reduced in amplitude by NTX in a dose-dependent manner. The toxin was slightly more potent on recombinant Drosophila/vertebrate hybrid receptors than on vertebrate homomeric (agr7) or heteromeric (agr4beta2) nicotinic AChRs. Block by NTX of the chicken agr7, chicken agr4beta2 and the SAD/beta2 and ALS/beta2 Drosophila/chicken hybrid receptors is in all cases non-competitive. Thus, the site of action on nicotinic AChRs of NTX, to which the insecticide Cartap is metabolised in insects, differs from that of the major nicotinic AChR-active insecticide, imidacloprid.
Keywords:Nicotinic acetylcholine receptor  Nereistoxin  Chicken   /content/m03gm5f8w7lvf6jd/xxlarge945.gif"   alt="  agr"   align="  BASELINE"   BORDER="  0"  >7 subunit  Chicken   /content/m03gm5f8w7lvf6jd/xxlarge945.gif"   alt="  agr"   align="  BASELINE"   BORDER="  0"  >4  /content/m03gm5f8w7lvf6jd/xxlarge946.gif"   alt="  beta"   align="  MIDDLE"   BORDER="  0"  >2 receptor   Drosophila melanogaster   Nicotinic receptor subunits (SAD, ALS)   Xenopus laevis oocytes
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