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Determinants of competitive antagonist sensitivity on neuronal nicotinic receptor beta subunits.
Harvey SC, Luetje CW.
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We constructed a series of chimeric and mutant neuronal nicotinic acetylcholine receptor beta subunits to map amino acid residues that determine sensitivity to competitive antagonists. The beta 2 and beta 4 subunits form pharmacologically distinct receptors when expressed in combination with the alpha 3 subunit in Xenopus oocytes. At equipotent acetylcholine concentrations, alpha 3 beta 2 is 56-fold more sensitive to blockage by dihydro-beta-erythroidine than is alpha 3 beta 4. The alpha 3 beta 2 combination is also sensitive to long-term blockade by neuronal bungarotoxin, whereas alpha 3 beta 4 is not. Pharmacological analysis of receptors formed by chimeric beta subunits reveals that amino acid residues that determine both dihydro-beta-erythroidine and neuronal bungarotoxin sensitivity are located within several sequence segments. The major determinant of sensitivity to both competitive antagonists is located between residues 54 and 63. A minor determinant of sensitivity to both antagonists lies between residues 1 and 54, whereas a minor determinant of NBT sensitivity lies between residues 74 and 80. Within region 54-63 of beta 2, mutant beta 2 subunits were used to identify threonine 59 as a residue critical in determining competitive antagonist sensitivity. Changing threonine 59 to lysine, as occurs in beta 4, causes a 9-fold decrease in dihydro-beta-erythroidine sensitivity and a 71-fold decrease in neuronal bungarotoxin sensitivity. Changing polar threonine 59 to negatively charged aspartate causes a 2.5-fold increase in neuronal bungarotoxin sensitivity and has no effect on dihydro-beta-erythroidine sensitivity.
Abramson,
An analog of lophotoxin reacts covalently with Tyr190 in the alpha-subunit of the nicotinic acetylcholine receptor.
1989, Pubmed
Abramson,
An analog of lophotoxin reacts covalently with Tyr190 in the alpha-subunit of the nicotinic acetylcholine receptor.
1989,
Pubmed Bertrand,
Pharmacological properties of the homomeric alpha 7 receptor.
1992,
Pubmed
,
Xenbase Blount,
Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor.
1989,
Pubmed Boulter,
Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.
1987,
Pubmed
,
Xenbase Cohen,
Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors.
1995,
Pubmed
,
Xenbase Corringer,
Identification of a new component of the agonist binding site of the nicotinic alpha 7 homooligomeric receptor.
1995,
Pubmed Craig,
The Cheng-Prusoff relationship: something lost in the translation.
1993,
Pubmed Czajkowski,
Negatively charged amino acid residues in the nicotinic receptor delta subunit that contribute to the binding of acetylcholine.
1993,
Pubmed
,
Xenbase Czajkowski,
Agonist binding site of Torpedo electric tissue nicotinic acetylcholine receptor. A negatively charged region of the delta subunit within 0.9 nm of the alpha subunit binding site disulfide.
1991,
Pubmed Dennis,
Amino acids of the Torpedo marmorata acetylcholine receptor alpha subunit labeled by a photoaffinity ligand for the acetylcholine binding site.
1988,
Pubmed Dewan,
Crystal structure of kappa-bungarotoxin at 2.3-A resolution.
1994,
Pubmed Duvoisin,
The functional diversity of the neuronal nicotinic acetylcholine receptors is increased by a novel subunit: beta 4.
1989,
Pubmed
,
Xenbase Elgoyhen,
Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells.
1994,
Pubmed
,
Xenbase Figl,
Regions of beta 4.beta 2 subunit chimeras that contribute to the agonist selectivity of neuronal nicotinic receptors.
1992,
Pubmed
,
Xenbase Fiordalisi,
Site-directed mutagenesis of kappa-bungarotoxin: implications for neuronal receptor specificity.
1994,
Pubmed Fu,
Competitive antagonists bridge the alpha-gamma subunit interface of the acetylcholine receptor through quaternary ammonium-aromatic interactions.
1994,
Pubmed Galzi,
Identification of a novel amino acid alpha-tyrosine 93 within the cholinergic ligands-binding sites of the acetylcholine receptor by photoaffinity labeling. Additional evidence for a three-loop model of the cholinergic ligands-binding sites.
1990,
Pubmed Halvorsen,
Affinity labeling of neuronal acetylcholine receptor subunits with an alpha-neurotoxin that blocks receptor function.
1987,
Pubmed Hussy,
Agonist and antagonist effects of nicotine on chick neuronal nicotinic receptors are defined by alpha and beta subunits.
1994,
Pubmed
,
Xenbase Kao,
Identification of the alpha subunit half-cystine specifically labeled by an affinity reagent for the acetylcholine receptor binding site.
1984,
Pubmed Leff,
Further concerns over Cheng-Prusoff analysis.
1993,
Pubmed Luetje,
Nicotine receptors in the mammalian brain.
1990,
Pubmed Luetje,
Neurotoxins distinguish between different neuronal nicotinic acetylcholine receptor subunit combinations.
1990,
Pubmed
,
Xenbase Luetje,
Mapping of ligand binding sites of neuronal nicotinic acetylcholine receptors using chimeric alpha subunits.
1993,
Pubmed
,
Xenbase Luetje,
Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors.
1991,
Pubmed
,
Xenbase Middleton,
Mapping of the acetylcholine binding site of the nicotinic acetylcholine receptor: [3H]nicotine as an agonist photoaffinity label.
1991,
Pubmed Nowak,
Nicotinic receptor binding site probed with unnatural amino acid incorporation in intact cells.
1995,
Pubmed
,
Xenbase Papke,
The amino terminal half of the nicotinic beta-subunit extracellular domain regulates the kinetics of inhibition by neuronal bungarotoxin.
1993,
Pubmed Papke,
Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.
1989,
Pubmed
,
Xenbase Pedersen,
d-Tubocurarine binding sites are located at alpha-gamma and alpha-delta subunit interfaces of the nicotinic acetylcholine receptor.
1990,
Pubmed Role,
Diversity in primary structure and function of neuronal nicotinic acetylcholine receptor channels.
1992,
Pubmed Sargent,
The diversity of neuronal nicotinic acetylcholine receptors.
1993,
Pubmed Sheridan,
The ensemble approach to distance geometry: application to the nicotinic pharmacophore.
1986,
Pubmed Sine,
Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of residues that determine curare selectivity.
1993,
Pubmed Wheeler,
Residues 1 to 80 of the N-terminal domain of the beta subunit confer neuronal bungarotoxin sensitivity and agonist selectivity on neuronal nicotinic receptors.
1993,
Pubmed
,
Xenbase Williams,
Binding of the nicotinic cholinergic antagonist, dihydro-beta-erythroidine, to rat brain tissue.
1984,
Pubmed
