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
| Autor: | Bruce N. Cohen, H A Lester, Antonio Figl, Norman Davidson, C. Labarca, M W Quick |
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| Rok vydání: | 1995 |
| Předmět: |
Agonist
Physiology medicine.drug_class Recombinant Fusion Proteins Xenopus Molecular Sequence Data Alpha (ethology) Cooperativity Biology Receptors Nicotinic Cytisine chemistry.chemical_compound medicine Animals Amino Acid Sequence Nicotinic Agonists Receptor Beta (finance) chemistry.chemical_classification Neurons Dose-Response Relationship Drug Articles Acetylcholine Amino acid Rats Electrophysiology Kinetics Nicotinic agonist chemistry Biochemistry Mutation Biophysics Oocytes Caltech Library Services |
| Zdroj: | The Journal of General Physiology |
| ISSN: | 0022-1295 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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