title: Calcium pathways such as cAMP modulate clothianidin action through activation of α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptors.
abstract: Clothianidin is a neonicotinoid insecticide developed in the early 2000s. We have recently demonstrated that it was a full agonist of α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptors expressed in the cockroach dorsal unpaired median neurons. Clothianidin was able to act as an agonist of imidacloprid-insensitive nAChR2 receptor and internal regulation of cAMP concentration modulated nAChR2 sensitivity to clothianidin. In the present study, we demonstrated that cAMP modulated the agonist action of clothianidin via α-bungarotoxin-sensitive and insensitive receptors. Clothianidin-induced current-voltage curves were dependent to clothianidin concentrations. At 10 μM clothianidin, increasing cAMP concentration induced a linear current-voltage curve. Clothianidin effects were blocked by 0.5 μM α-bungarotoxin suggesting that cAMP modulation occurred through α-bungarotoxin-sensitive receptors. At 1 mM clothianidin, cAMP effects were associated to α-bungarotoxin-insensitive receptors because clothianidin-induced currents were blocked by 5 μM mecamylamine and 20 μM d-tubocurarine. In addition, we found that application of 1mM clothianidin induced a strong increase of intracellular calcium concentration. These data reinforced the finding that calcium pathways including cAMP modulated clothianidin action on insect nicotinic acetylcholine receptors. We proposed that intracellular calcium pathways such as cAMP could be a target to modulate the mode of action of neonicotinoid insecticides.
authors: Université d'Angers, Laboratoire Récepteurs et Canaux Ioniques Membranaires (RCIM), UPRES EA 2647/USC INRA 1330, UFR de Sciences, 2 Bd. Lavoisier, 49045 Angers, France.
authors: Delphine
authors: D
authors: Calas-List
authors: Olivier
authors: O
authors: List
authors: Sophie
authors: S
authors: Quinchard
authors: Steeve H
authors: SH
authors: Thany
mesh_terms: D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D019476:Insect Proteins / Q000187:drug effects* / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D000073943:Neonicotinoids; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010526:Periplaneta; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists* / Q000378:metabolism
chemical_list: D002038:Bungarotoxins; D006146:Guanidines; D019476:Insect Proteins; D007306:Insecticides; D000073943:Neonicotinoids; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013844:Thiazoles; D064569:alpha7 Nicotinic Acetylcholine Receptor; C480342:clothianidin; D000242:Cyclic AMP