Desensitizing and non-desensitizing subtypes of alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors in cockroach neurons.
Two alpha-bungarotoxin-sensitive nicotinic receptor subtypes in cockroach neurons are identified as desensitizing (nAChD), selectively inhibitable with 100 nM imidacloprid, and non-desensitizing (nAChN), selectively inhibitable with 100 pM methyllycaconitine. Although the desensitization rate of nAChD receptors is highly variable, pharmacology is largely independent of desensitization rate. Because desensitized states tightly bind agonists, nAChD receptors are potently inhibited by neonicotinoids and specifically measured in radiolabeled imidacloprid binding assays. However, they are not usually detected in binding assays with radiolabeled alpha-bungarotoxin, which has a Kd for the resting state of 21 nM, but binds poorly to desensitized states often present in binding assays. In contrast, nAChN receptors are specifically measured in binding assays with radiolabeled alpha-bungarotoxin, which binds them with a Kd of 1.3 nM. nAChN receptors are activated by neonicotinoids at micromolar concentrations, and allosterically by spinosyn A, with an EC50 of 27 nM. Spinosyn A weakly antagonizes nAChD receptors -23% at 10 microM. The roles of the two nAChR subtypes in insecticide poisoning are discussed.
Salgado
Vincent L
VL
Bayer CropScience AG, Global Biology Insecticides, Alfred-Nobel-Strasse 50, D-40789 Monheim am Rhein, Germany. vincent.salgado@bayercropscience.com
Saar
Raimund
R
D000109:Acetylcholine / Q000378:metabolism; D000157:Aconitine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism*; D003058:Cockroaches / Q000378:metabolism*; D004079:Dihydro-beta-Erythroidine / Q000378:metabolism; D004594:Electrophysiology; D006146:Guanidines / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007700:Kinetics; D018942:Macrolides / Q000378:metabolism; D000073943:Neonicotinoids; D009474:Neurons / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000378:metabolism*; D009574:Nitro Compounds; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D013844:Thiazoles
D002038:Bungarotoxins; D006146:Guanidines; D007093:Imidazoles; D018942:Macrolides; D000073943:Neonicotinoids; D018733:Nicotinic Antagonists; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; D013844:Thiazoles; C114883:spinosyn A; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; C480342:clothianidin; C082359:imidacloprid; D001285:Atropine; D000109:Acetylcholine; D000157:Aconitine