title: Quinuclidine compounds differently act as agonists of Kenyon cell nicotinic acetylcholine receptors and induced distinct effect on insect ganglionic depolarizations.
abstract: We have recently demonstrated that a new quinuclidine benzamide compound named LMA10203 acted as an agonist of insect nicotinic acetylcholine receptors. Its specific pharmacological profile on cockroach dorsal unpaired median neurons (DUM) helped to identify alpha-bungarotoxin-insensitive nAChR2 receptors. In the present study, we tested its effect on cockroach Kenyon cells. We found that it induced an inward current demonstrating that it bounds to nicotinic acetylcholine receptors expressed on Kenyon cells. Interestingly, LMA10203-induced currents were completely blocked by the nicotinic antagonist α-bungarotoxin. We suggested that LMA10203 effect occurred through the activation of α-bungarotoxin-sensitive receptors and did not involve α-bungarotoxin-insensitive nAChR2, previously identified in DUM neurons. In addition, we have synthesized two new compounds, LMA10210 and LMA10211, and compared their effects on Kenyon cells. These compounds were members of the 3-quinuclidinyl benzamide or benzoate families. Interestingly, 1 mM LMA10210 was not able to induce an inward current on Kenyon cells compared to LMA10211. Similarly, we did not find any significant effect of LMA10210 on cockroach ganglionic depolarization, whereas these three compounds were able to induce an effect on the central nervous system of the third instar M. domestica larvae. Our data suggested that these three compounds could bind to distinct cockroach nicotinic acetylcholine receptors.
authors.affiliation: CEISAM UMR CNRS 6230, UFR des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, 44322, Nantes, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Mathé-Allainmat
authors.forename: Daniel
authors.initials: D
authors.lastname: Swale
authors.forename: Xavier
authors.initials: X
authors.lastname: Leray
authors.forename: Yassine
authors.initials: Y
authors.lastname: Benzidane
authors.forename: Jacques
authors.initials: J
authors.lastname: Lebreton
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bloomquist
authors.forename: Steeve H
authors.initials: SH
authors.lastname: Thany
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003058:Cockroaches; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D001549:Benzamides; C573733:LMA 10203; D018722:Nicotinic Agonists; D011812:Quinuclidines; D011978:Receptors, Nicotinic