Actions of vesamicol on an alpha-bungarotoxin-sensitive neuronal nicotinic acetylcholine receptor.
Electrophysiology and binding studies were used to determine the actions of vesamicol [2-(4-phenylpiperidino)cyclohexanol (AH5183)] on an alpha-bungarotoxin-sensitive, neuronal nicotinic acetylcholine receptor in the nervous system of the cockroach, Periplaneta americana. Electrophysiological studies on an identified motor neurone revealed a reversible blocking action of (+/-)-vesamicol on the response to ionophoretically applied acetylcholine with an IC50 value of 8.0 x 10(-6) mol1(-1). The block was weakly voltage-dependent over the membrane potential range of -50 mV to -90 mV, and appeared to be non-competitive. No difference in potency was observed between the resolved stereoisomers. (+/-)-Vesamicol was found to suppress specific binding of 125I-labelled alpha-bungarotoxin to cockroach nervous tissue with an IC50 value of 5.1 x 10(-3) mol1(-1) and an estimated Hill coefficient of 0.73. Differences in the Hill coefficients were found when the resolved stereoisomers were tested separately. These data provide the first demonstration of a blocking action by vesamicol of a neuronal nicotinic acetylcholine receptor.
Buckingham
S D
SD
AFRC Laboratory of Molecular Signalling, University of Cambridge, UK.
Lummis
S C
SC
Balk
M L
ML
Schroeder
M
M
Sattelle
D B
DB
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009046:Motor Neurons; D018733:Nicotinic Antagonists; D010276:Parasympatholytics; D010526:Periplaneta; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013237:Stereoisomerism
D002038:Bungarotoxins; D018733:Nicotinic Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D011978:Receptors, Nicotinic; C006189:vesamicol