ArticleThe Journal of general physiology1995
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.
Article in The Journal of general physiology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 52 citations in OpenAlex.
- Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators.Molecules (Basel, Switzerland) · 2023Review
- Varying Chirality Across Nicotinic Acetylcholine Receptor Subtypes: Selective Binding of Quinuclidine Triazole Compounds.ACS medicinal chemistry letters · 2016Article
- Specificity determinants of allosteric modulation in the neuronal nicotinic acetylcholine receptor: a fine line between inhibition and potentiation.Molecular pharmacology · 2012Article
- Computational modeling study of human nicotinic acetylcholine receptor for developing new drugs in the treatment of alcoholism.Interdisciplinary sciences, computational life sciences · 2009Article
- Photoaffinity labeling the agonist binding domain of alpha4beta4 and alpha4beta2 neuronal nicotinic acetylcholine receptors with [(125)I]epibatidine and 5[(125)I]A-85380.Biochimica et biophysica acta · 2009Article
- The positive allosteric modulator morantel binds at noncanonical subunit interfaces of neuronal nicotinic acetylcholine receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Novel seizure phenotype and sleep disruptions in knock-in mice with hypersensitive alpha 4* nicotinic receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
- A structural model of agonist binding to the alpha3beta4 neuronal nicotinic receptor.British journal of pharmacology · 2003Article
- Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian alpha4beta2 acetylcholine response.The Journal of physiology · 2003Article
- Models of the extracellular domain of the nicotinic receptors and of agonist- and Ca2+-binding sites.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Two mutations linked to nocturnal frontal lobe epilepsy cause use-dependent potentiation of the nicotinic ACh response.The Journal of physiology · 1998Article
- Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1997Article
- Recombinant nicotinic receptors, expressed in Xenopus oocytes, do not resemble native rat sympathetic ganglion receptors in single-channel behaviour.The Journal of physiology · 1997Article
- Determinants of competitive antagonist sensitivity on neuronal nicotinic receptor beta subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1996Article
- Voltage-jump relaxation kinetics for wild-type and chimeric beta subunits of neuronal nicotinic receptors.The Journal of general physiology · 1996Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits to locate the regions that contribute to differences between the acetylcholine (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an EC50 for ACh approximately 20-fold less than the EC50 of the alpha 3 beta 4 receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the first 120 residues convert the EC50 for ACh from one wild-type value to the other. Exchanging just beta 2:104-120 for the corresponding region of beta 4 shifts the EC50 of ACh dose-response relationship in the expected direction but does not completely convert the EC50 of the dose-response relationship from one wild-type value to the other. However, substitutions in the beta 2:104-120 region do account for the relative sensitivity of the alpha 3 beta 2 receptor to cytisine, tetramethylammonium, and ACh. The expression of beta 4-like (strong) cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2-like values. The results suggest that amino acids within the first 120 residues of beta 2 and the corresponding region of beta 4 contribute to an agonist binding site that bridges the alpha and beta subunits in neuronal nicotinic receptors.
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