Actions of a series of bisquaternary compounds on nicotinic acetylcholine receptors in insects: ligand binding and electrophysiological studies.
A series of bisquaternary ammoniums, with chain lengths of between 4-12 carbon atoms (C4-C12), have been tested for their ability to block acetylcholine-induced responses in the fast coxal depressor motor neurone (Df) of the cockroach (Periplaneta americana) and to displace [125I]alpha-bungarotoxin from membrane preparations of the CNS of the cockroach. The physiological studies showed that tetramethonium was inactive, whereas hexa-, octa- and dodecamethonium showed an enhanced ability to block acetylcholine-induced responses as the chain length increased. Decamethonium resulted in a slight increase in acetylcholine-induced depolarizations. Ligand binding studies showed that the ability of the compounds to inhibit the specific binding of [125I]alpha-bungarotoxin increased with size from C4-C12. The results show that neuronal nicotinic receptors in insects differ in aspects of their pharmacology from both the major subclasses of nicotinic receptors of vertebrates.
Lummis
S C
SC
Department of Zoology, University of Cambridge, U.K.
Buckingham
S D
SD
Balk
M L
ML
Holyoke
C W
CW
Sattelle
D B
DB
D000818:Animals; D008725:Bis-Trimethylammonium Compounds / Q000494:pharmacology*; D002038:Bungarotoxins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003058:Cockroaches / Q000502:physiology*; D005724:Ganglia / Q000502:physiology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D008725:Bis-Trimethylammonium Compounds; D002038:Bungarotoxins; D008024:Ligands; D011978:Receptors, Nicotinic