A uniquely selective inhibitor of the mammalian fetal neuromuscular nicotinic acetylcholine receptor.
We have purified and characterized a novel conotoxin from the venom of Conus obscurus, which has the unique property of selectively and potently inhibiting the fetal form of the mammalian neuromuscular nicotinic acetylcholine receptor (nAChR) (alpha1beta1gammadelta-subunits). Although this conotoxin, alphaA-conotoxin OIVB (alphaA-OIVB), is a high-affinity antagonist (IC50 of 56 nm) of the fetal muscle nAChR, it has >1800-fold lower affinity for the adult muscle nAChR (alpha1beta1epsilondelta-subunits) and virtually no inhibitory activity at a high concentration on various neuronal nAChRs (IC50 > 100 microm in all cases). The peptide (amino acid sequence, CCGVONAACPOCVCNKTCG), with three disulfide bonds, has been chemically synthesized in a biologically active form. Although the neuromuscular nAChRs are perhaps the most extensively characterized of the receptors/ion channels of the nervous system, the precise physiological roles of the fetal form of the muscle nAChR are essentially unknown.alphaA-OIVB is a potentially important tool for delineating the functional roles ofalpha1beta1gammadelta receptors in normal development, as well as in various adult tissues and in pathological states. In addition to its potential as a research tool, alphaA-OIVB may have some direct biomedical applications.
Teichert
Russell W
RW
Department of Biology, University of Utah, Salt lake City, Utah 84112, USA. teichert@biology.utah.edu
Rivier
Jean
J
Torres
Josep
J
Dykert
John
J
Miller
Charleen
C
Olivera
Baldomero M
BM
D000328:Adult; D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D020916:Conotoxins / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D005333:Fetus; D006054:Goldfish; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000187:drug effects* / Q000196:embryology*; D009469:Neuromuscular Junction / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D010243:Paralysis / Q000139:chemically induced; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000145:classification / Q000187:drug effects*; D011994:Recombinant Proteins; D012908:Snails / Q000737:chemistry; D014981:Xenopus
D020916:Conotoxins; D008024:Ligands; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; C502896:alphaA-conotoxin OIVB, Conus obscurus