title: alpha-Conotoxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors.
abstract: Muscle subtypes of the nicotinic acetylcholine receptor contain two acetylcholine binding sites that can be distinguished pharmacologically. The affinities of several alpha-conotoxins for the two acetylcholine binding sites on nicotinic receptors from BC3H1 cells and Torpedo electric organ were investigated. alpha-Conotoxins MI, GI, and SIA each inhibited the binding of 125I-alpha-bungarotoxin to nicotinic acetylcholine receptors on BC3H1 cells with two distinct and independent affinities, which differed by > 10,000-fold. The affinities of alpha-conotoxins SI and SII were significantly lower and the differences in the affinities of each of these toxins for the two sites were < 400-fold. alpha-Conotoxins MI, GI, SIA, and SI had higher affinity for the acetylcholine binding site near the alpha/delta subunit interface of nicotinic receptors from BC3H1 cells. However, when assessed using nicotinic receptors from Torpedo electric organ, alpha-conotoxin MI displayed higher affinity for the acetylcholine binding site near the alpha/gamma subunit interface. These observations suggest that species variations in the sequences of the gamma and delta subunits resulted in a dramatic reversal of the relative affinities of the alpha-conotoxins for each acetylcholine binding site. Some of the practical implications of these observations are discussed.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Pittsburgh, Pennsylvania 15261, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Groebe
authors.forename: J M
authors.initials: JM
authors.lastname: Dumm
authors.forename: E S
authors.initials: ES
authors.lastname: Levitan
authors.forename: S N
authors.initials: SN
authors.lastname: Abramson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014101:Torpedo
chemical_list: D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; D000109:Acetylcholine